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Tumor Types (tumor + type)
Kinds of Tumor Types Selected AbstractsMRI tumor characterization using Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ), a protein-avid contrast agentCONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2006Hans-Jürgen Raatschen Abstract The rationale and objectives were to define the MRI tumor-characterizing potential of a new protein-avid contrast agent, Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05,mmol,Gd,kg,1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N -ethyl- N -nitrosourea (ENU), 45,250,mg,kg,1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two-compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (KPS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff,Bloom,Richardson score) and location of necrosis. Eighteen tumor-bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. KPS and fEV*, but not fPV obtained from tumors correlated significantly (p,<,0.05) with the SBR tumor grade, r,=,0.65 and 0.56, respectively. Estimates for KPS and fEV* but not fPV were significantly lower in a group consisting of benign and low-grade malignant tumors compared with the group of less-differentiated high-grade tumors (1.61,±,0.64 vs 3.37,±,1.49, p,<,0.01; 0.45,±,0.17 vs 0.78,±,0.24, p,<,0.01; and 0.076,±,0.048 vs 0.121,±,0.088, p,=,0.24, respectively). It is concluded that the protein-avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low-grade malignant lesions from high-grade cancers. Copyright © 2006 John Wiley & Sons, Ltd. [source] Immunohistochemical Stains in Mohs Surgery: A ReviewDERMATOLOGIC SURGERY, Issue 7 2009DONALD STRANAHAN MD BACKGROUND During Mohs surgery, there are instances in which residual tumor cells may be difficult to detect, thereby increasing the risk of incomplete excision and tumor recurrence. It is possible to employ immunohistochemical techniques as an adjunct to routine hematoxylin and eosin staining to aid in ensuring negative margins. OBJECTIVE To review the literature regarding the use of immunostains in Mohs surgery. RESULTS Various immunostains have proved useful in detecting tumor cells in various malignancies, including melanoma, basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, extramammary Paget's disease, primary cutaneous mucinous carcinoma, granular cell tumor, and trichilemmal carcinoma. CONCLUSIONS In this article, we review immunohistochemical stains that have been employed in Mohs micrographic surgery and evaluate their utility in enhancing detection of residual tumors with respect to tumor type, particularly in situations in which detection of residual tumor may be difficult. [source] Mohs Micrographic Surgery in the Treatment of Rare Aggressive Cutaneous Tumors: The Geisinger ExperienceDERMATOLOGIC SURGERY, Issue 3 2007CHADWICK JOHN THOMAS MD BACKGROUND Mohs micrographic surgery (MMS) offers high cure rates and maximum tissue preservation in the treatment of more common cutaneous malignancies, but its effectiveness in rare aggressive tumors is poorly defined. OBJECTIVE Evaluate the effectiveness of MMS in the treatment of six rare aggressive cutaneous malignancies as seen by Mohs surgeons working at a referral center. METHODS Retrospective chart review of 26,000 cases treated with MMS at the Geisinger Medical Center Department of Dermatology during a 16-year period with the following diagnoses: poorly differentiated squamous cell carcinoma (PDSCC), dermatofibrosarcoma protuberans (DFSP), microcystic adnexal carcinoma (MAC), extramammary Paget's disease (EMPD), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SEB CA). Patient demographic data, tumor measurements, treatment characteristics, and marginal recurrence rates were compiled and evaluated. RESULTS The mean numbers of cases identified per year for each tumor type were as follows: PDSCC, 6.19; DFSP, 2.44; MAC, 1.63; and EMPD, 0.63. For PDSCC, 85 cases were available for follow-up with a local recurrence rate of 6% at a mean follow-up time of 45 months. For DFSP, there were 35 cases with no local recurrence at a mean follow-up of 39 months. For MAC, there were 25 cases with a local recurrence rate of 12% at a mean follow-up of 39 months. For EMPD, there were 10 cases with no local recurrences at a mean follow-up of 34 months. CONCLUSIONS Collectively, our data on PDSCC, DFSP, MAC, and EMPD, combined with other studies in the literature, show that MMS is the most effective therapy for these rare aggressive cutaneous malignancies. [source] TEACHING DEEP CANNULATION OF THE BILE DUCT DURING ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHYDIGESTIVE ENDOSCOPY, Issue 4 2007Kiichi Tamada When performing endoscopic retrograde cholangiopancreatography (ERCP), the smooth introduction of the duodenoscope into the papilla of Vater, an appropriate view of the papilla of Vater, and deep cannulation of the bile duct are essential. The operator must know the difference between the side-viewing endoscope and the forward-viewing endoscope. The rotation of the body and the left arm of the operator, switching with the left wrist, and dialing of the endoscope are essential for appropriately viewing the papilla of Vater. When training operators to do ERCP, a model is useful for helping them understand basic handling. The approach to deep cannulation of the bile duct should be selected based on the type of papilla (slit type, onion type, tongue protrusion type, flat type, and tumor type). Cannulation is more difficult in patients with the tongue protrusion-type of papilla than with a slit type, onion type, or tumor type. According to previous reports, therapeutic ERCP requires the ability to cannulate the common bile duct deeply 80% of the time; 180 to 200 supervised ERCP are necessary to achieve this success rate. [source] Estrogen and progesterone receptors in esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 4 2008R. Kalayarasan SUMMARY., Information is sparse and contradictory in the literature regarding the role of estrogen receptor (ER) and progesterone receptor (PR) in esophageal carcinoma. This study was conducted over a period of 18 months from September 2004 with the primary aim of determining the PR, ER alpha (ER,) and ER beta (ER,) status of esophageal carcinoma and normal esophageal mucosa (NEM). The receptor status was correlated with tumor type, tumor differentiation and tumor stage. A total of 45 patients with histologically proven squamous cell carcinoma (SCC) (n = 30) and adenocarcinoma (AC) (n = 15) were studied. Receptor status was detected by immunohistochemistry (IHC) and semiquantitative assessment was done by quick score method of endoscopic biopsy specimens. The mean age for SCC and AC were not significantly different. The gender ratio in favor of males was 3 : 2 for SCC and 4 : 1 for AC. None of the specimens from SCC or AC showed positivity for PR both in NEM and tumor tissue. Likewise none of the specimens were positive for ER, by IHC. The mean ER, score for AC was significantly higher than SCC. For SCC it was seen that ER, positivity in tumor cells increases with dedifferentiation and increasing tumor stage. This trend was seen for AC as well. ER, is over-expressed in poorly differentiated SCC and AC compared to NEM. Thus ER, may be a marker for poor biological behavior, that is dedifferentiation or higher stage of disease. In view of these findings we propose a large-scale prospective, longitudinal interventional study using selective estrogen modulators. [source] Cutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancerGENES, CHROMOSOMES AND CANCER, Issue 2 2008Sonja Hahtola Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source] APC/CTNNB1 (,-catenin) pathway alterations in human prostate cancersGENES, CHROMOSOMES AND CANCER, Issue 1 2002Amy V. Gerstein Genetic alterations serve as beacons for the involvement of specific pathways in tumorigenesis. It was previously shown that 5% of prostate tumors harbor CTNNB1 mutations, suggesting that this tumor type may involve a deregulated APC/CTNNB1 pathway. To explore this possibility further, we searched for mutations in genes implicated in this pathway in 22 samples that included cell lines, xenografts, and primary tumors. We identified seven alterations: two in CTNNB1, three in APC, and two in hTRCP1 (also known as BTRC) which controls the degradation of CTNNB1. Alterations in the CTNNB1 regulatory domain, APC, and hTRCP1 were mutually exclusive, consistent with their equivalent effects on CTNNB1 stability. These results suggest that CTNNB1 signaling plays a critical role in the development of a significant fraction of prostate cancers. Moreover, they provide the first evidence that hTRCP1 plays a role in human neoplasia. © 2002 Wiley-Liss, Inc. [source] Sentinel node biopsy and head and neck tumors,Where do we stand today?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2006FCAP, Kenneth O. Devaney MD Abstract Background. Sentinel lymph node sampling may be studied profitably in series of patients with 1 tumor type, such as breast carcinoma, in 1 anatomic locale. The present work analyzes the efficacy of sentinel node sampling in a pathologically diverse group of lesions from an anatomically diverse region such as the head and neck; however, there are risks conflating the findings in different tumors with radically different behaviors, in the process producing muddled data. This report reviews the head and neck experience with sentinel sampling and concludes that certain tumor types that have a known propensity for aggressive behavior are the best candidates for trials employing sentinel node sampling; candidates include many cutaneous melanomas of the head and neck, oropharyngeal squamous carcinomas, and selected thyroid carcinomas. Despite the growing popularity of sentinel node sampling in a variety of regions of the body, however, at this juncture this technique remains an investigational procedure, pending demonstration of a tangible improvement in patient outcome through its use. It is recommended that studies of the efficacy of this technique strive, whenever possible, to segregate results of different tumor types in different head and neck locales from one another so as to produce more focused findings for discrete types of malignancies, and not group together tumor types that may in reality exhibit different biological behaviors. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Combined endovascular and surgical treatment of head and neck paragangliomas,A team approach,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2002Mark S. Persky MD Abstract Background Paragangliomas are highly vascular tumors of neural crest origin that involve the walls of blood vessels or specific nerves within the head and neck. They may be multicentric, and they are rarely malignant. Surgery is the preferred treatment, and these tumors frequently extend to the skull base. There has been controversy concerning the role of preoperative angiography and embolization of these tumors and the benefits that these procedures offer in the evaluation and management of paragangliomas. Methods Forty-seven patients with 53 paragangliomas were treated from the period of 1990,2000. Initial evaluation usually included CT and/or MRI. All patients underwent bilateral carotid angiography, embolization of the tumor nidus, and cerebral angiography to define the patency of the circle of Willis. Carotid occlusion studies were performed with the patient under neuroleptic anesthesia when indicated. The tumors were excised within 48 hours of embolization. Results Carotid body tumors represented the most common paraganglioma, accounting for 28 tumors (53%). All patients underwent angiography and embolization with six patients (13%), demonstrating complications (three of these patients had embolized tumor involving the affected nerves). Cerebral angiography was performed in 28 patients, and 5 of these patients underwent and tolerated carotid occlusion studies. The range of mean blood loss according to tumor type was 450 to 517 mL. Postoperative cranial nerve dysfunction depended on the tumor type resected. Carotid body tumor surgery frequently required sympathetic chain resection (21%), with jugular and vagal paraganglioma removal frequently resulting in lower cranial nerve resection. These patients required various modes of postoperative rehabilitation, especially vocal cord medialization and swallowing therapy. Conclusions The combined endovascular and surgical treatment of paragangliomas is acceptably safe and effective for treating these highly vascular neoplasms. Adequate resection may often require sacrifice of one or more cranial nerves, and appropriate rehabilitation is important in the treatment regimen. © 2002 Wiley Periodicals, Inc. [source] Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapyHEMATOLOGICAL ONCOLOGY, Issue 4 2003Timothy J. Littlewood Abstract Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb ,2,g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached ,12,g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan,Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan,Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3,g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan,Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies. Copyright © 2004 John Wiley & Sons, Ltd. [source] Mutation rate of MAP2K4/MKK4 in breast carcinoma ,,HUMAN MUTATION, Issue 1 2002Gloria H. Su Abstract The stress-activated protein kinase (SAPK) pathways represent phosphorylation cascades that convey pro-apoptotic signals. The relevant inputs include Ras proteins as well as exposure of cells to ultraviolet light, tumor-necrosis factor, and other stress-related inputs. The mitogen-activated protein kinase kinase (MAPKK) homolog MAP2K4 (MKK4, SEK, JNKK1) is a centrally-placed mediator of the SAPK pathways. MAP2K4 mutations or homozygous deletions are reported in about 5% of a wide variety of tumor types. The exception is breast cancer, where genetic inactivation in 3 of 22 (15%) cell lines had suggested that the mutational involvement of MAP2K4 might be accentuated in this tumor type. This finding might have represented an important difference, or solely a chance numerical variation. To address this question, we studied an independent panel of 20 breast cancer cell lines and xenografts for MAP2K4 alterations. We found a splice acceptor mutation accompanied by loss of the other allele in the cell line MPE600. This was the sole alteration in this panel (5% of tumors). These data seem to re-establish a rather consistent rate of genetic inactivation of MAP2K4 among most tumor types, including breast cancer. The genetic evaluation of other mediators of the SAPK pathways might offer insight into a promising, but as yet poorly defined, tumor-suppressive system. © 2001 Wiley-Liss, Inc. [source] Elucidation of a protein signature discriminating six common types of adenocarcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 4 2007Gregory C. Bloom Abstract Pathologists are commonly facing the problem of attempting to identify the site of origin of a metastatic cancer when no primary tumor has been identified, yet few markers have been identified to date. Multitumor classifiers based on microarray based RNA expression have recently been described. Here we describe the first approximation of a tumor classifier based entirely on protein expression quantified by two-dimensional gel electrophoresis (2DE). The 2DE was used to analyze the proteomic expression pattern of 77 similarly appearing (using histomorphology) adenocarcinomas encompassing 6 types or sites of origin: ovary, colon, kidney, breast, lung and stomach. Discriminating sets of proteins were identified and used to train an artificial neural network (ANN). A leave-one-out cross validation (LOOCV) method was used to test the ability of the constructed network to predict the single held out sample from each iteration with a maximum predictive accuracy of 87% and an average predictive accuracy of 82% over the range of proteins chosen for its construction. These findings demonstrate the use of proteomics to construct a highly accurate ANN-based classifier for the detection of an individual tumor type, as well as distinguishing between 6 common tumor types in an unknown primary diagnosis setting. © 2006 Wiley-Liss, Inc. [source] Maternal medication use and the risk of brain tumors in the offspring: The SEARCH international case-control studyINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Amanda H. Cardy Abstract N -nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R1NNO·COR2), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (,5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring. © 2005 Wiley-Liss, Inc. [source] Skin cancer trends in northern JordanINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2006Abdel K. Omari MD Background, The Jordan Cancer Registry was established in 1996, since which time all cases of cancer have been reported and registered. We have used this registry to perform the first analysis of skin cancer in northern Jordan and to compare our findings with those of published reports from other regions. Methods, All histopathologically proven cases of skin cancer, reported during the years 1997 through 2001, were reviewed. Information regarding tumor type, age, gender, and anatomical location was collected. Results, A total of 272 cases of malignant skin tumors were diagnosed between the years 1997 and 2001. Basal cell carcinoma (BCC) was the commonest type, representing 52.9% of all skin cancers. Females were more frequently affected than males, with age-adjusted incidence rates of 23.3 and 19.7 per 100,000 of population, respectively. Squamous cell carcinoma (SCC) comprised 26.4% of the total, its age-adjusted incidence rate per 100,000 of population being 14.2 for males and 6.18 for females. the incidence rate increased in males and decreased in females during the study period. The incidence of both BCC and SCC increased with age. The head and neck region was the commonest site affected by both types of cancer. Malignant melanoma (MM) comprised 11.39% of all skin cancer cases, with a female to male ratio of 1.2 : 1. The median age at onset for female patients was 49 years while that for males was 70 years, and the commonest site affected was the lower limbs, followed by the trunk. Conclusions, In Jordan, sun-related skin cancers have relatively low incidences and a rather stable pattern, compared with other areas with similar climate and skin phenotypes. [source] Expression patterns of hair and epithelial keratins and transcription factors HOXC13, LEF1, and ,-catenin in a malignant pilomatricoma: a histological and immunohistochemical studyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2006Bernard Cribier Background:, We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co-expression of the LEF1/,-catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078). Methods:, Formalin-fixed paraffin sections of the tumor were examined using a panel of mono- and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and ,-catenin. Results:, Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co-expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/,-catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co-expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls. Conclusions:, Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co-expression and disrupted hHa1/,-catenin,LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor. [source] BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Biologic and clinical variations of adenocarcinoma at the esophago,gastric junction: Relevance of a topographic-anatomic subclassification,JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2005J. Rüdiger Siewert Abstract A topographic-anatomic subclassification of adenocarcinomas of the esophago,gastric junction (AEG) in distal esophageal adenocarcinoma (AEG Type I), true carcinoma of the cardia (AEG Type II), and subcardial gastric cancer (AEG Type III) was introduced in 1987 and is now increasingly accepted and used worldwide. Our experience with now more than 1,300 resected AEG tumors indicates that the subtypes differ markedly in terms of surgical epidemiology, histogenesis and histomorphologic tumor characteristics. While underlying specialized intestinal metaplasia can be found in basically all patients with AEG Type I tumors, this is uncommon in Type II tumors and virtually absent in Type III tumors. Stage distribution and overall long-term survival after surgical resection also shows marked differences between the AEG subtypes. Surgical treatment strategies based on tumor type allow a differentiated approach and result in survival rates superior to those reported with other approaches. The subclassification of AEG tumors thus provides a useful tool for the selection of the surgical procedure and allows a better comparison of treatment results. J. Surg. Oncol. 2005;90:139,146. © 2005 Wiley-Liss, Inc. [source] Canine Digital Tumors: A Veterinary Cooperative Oncology Group Retrospective Study of 64 DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2005Carolyn J. Henry We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P± .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease. [source] Treatment of canine hemangiopericytomas with photodynamic therapyLASERS IN SURGERY AND MEDICINE, Issue 1 2001Dudley L. McCaw DVM Abstract Background and Objective Canine hemangiopericytomas are a commonly occurring neoplasm with a clinical course of recurrence after surgical removal. This study sought to evaluate Photochlor (HPPH) photodynamic therapy (HPPH-PDT) as an adjuvant therapy to prevent recurrence of tumor after surgical removal. Study Design/Materials and Methods Sixteen dogs with naturally occurring hemangiopericytomas were treated with surgical removal of the tumor followed by PDT using Photochlor as the photosensitizer. Photochlor was injected intravenously at a dose of 0.3,mg/kg. Forty-eight hours later the treatment consisted of surgical removal of the tumor followed by HPPH-PDT. Results Nine dogs (56%) had recurrence of tumor from 2 to 29 (median 9) months after treatment. These results are comparable or not as good as other forms of therapy. Conclusions Photochlor photodynamic therapy applied after surgery appears to have no advantage over other forms of therapy in regards to preventing recurrence. Delayed wound healing and infections are problematic and make HPPH-PDT an undesirable addition to surgery for the treatment of this tumor type. Lasers Surg. Med. 29:23,26, 2001. © 2001 Wiley-Liss, Inc. [source] In vitro studies of steroid hormones in neurofibromatosis 1 tumors and schwann cellsMOLECULAR CARCINOGENESIS, Issue 7 2007Lauren Fishbein Abstract The most common NF1 feature is the benign neurofibroma, which consists predominantly of Schwann cells. Dermal neurofibromas usually arise during puberty and increase in number throughout adulthood. Plexiform neurofibromas, associated with larger nerves, are often congenital and can be life threatening. Malignant peripheral nerve sheath tumors (MPNST) in NF1 are believed to arise from plexiforms in 5%,10% of patients. There are reports of increased potential for malignant transformation of plexiform tumors and increase in dermal neurofibromas, during pregnancy. These observations suggest that steroid hormones influence neurofibroma growth, and our work is the first to examine steroid hormone receptor expression and ligand-mediated cell growth and survival in normal human Schwann cells and neurofibroma-derived Schwann cell cultures. Immunohistochemistry and real-time PCR showed that estrogen receptors (ERs), progesterone receptor (PR), and androgen receptor are differentially expressed in primary neurofibromas and in NF1 tumor-derived Schwann cell cultures compared to normal Schwann cells. However, there is substantial heterogeneity, with no clear divisions based on tumor type or gender. The in vitro effects of steroid hormone receptor ligands on proliferation and apoptosis of early passage NF1 tumor-derived Schwann cell cultures were compared to normal Schwann cell cultures. Some statistically significant changes in proliferation and apoptosis were found, also showing heterogeneity across groups and ligands. Overall, the changes are consistent with increased cell accumulation. Our data suggest that steroid hormones can directly influence neurofibroma initiation or progression by acting through their cognate receptor, but that these effects may only apply to a subset of tumors, in either gender. © 2007 Wiley-Liss, Inc. [source] Low grade diffuse gliomas: Shared cellular composition and morphometric differencesNEUROPATHOLOGY, Issue 5 2008Sawako Kinjo Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy-eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas-Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software "Gunmetry." Twenty-two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis. [source] Pathology of soft-tissue tumors: Daily diagnosis, molecular cytogenetics and experimental approachPATHOLOGY INTERNATIONAL, Issue 8 2009Hiroshi Iwasaki This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-, may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas. [source] BI-69A11-mediated inhibition of AKT leads to effective regression of xenograft melanomaPIGMENT CELL & MELANOMA RESEARCH, Issue 2 2009Supriya Gaitonde Summary The AKT/PKB pathway plays a central role in tumor development and progression and is often up-regulated in different tumor types, including melanomas. We have recently reported on the in silico approach to identify putative inhibitors for AKT/PKB. Of the reported hits, we selected BI-69A11, a compound which was shown to inhibit AKT activity in in vitro kinase assays. Analysis of BI-69A11 was performed in melanoma cells, a tumor type that commonly exhibits up-regulation of AKT. Treatment of the UACC903 human melanoma cells, harboring the PTEN mutation, with BI-69A11 caused efficient inhibition of AKT S473 phosphorylation with concomitant inhibition of AKT phosphorylation of PRAS40. Treatment of melanoma cells with BI-69A11 also reduced AKT protein expression, which coincided with inhibition of AKT association with HSP-90. BI-69A11 treatment not only caused cell death of melanoma, but also prostate tumor cell lines. Notably, the effect of BI-69A11 on cell death was more pronounced in cells that express an active form of AKT. Significantly, intra-peritoneal injection of BI-69A11 caused effective regression of melanoma tumor xenografts, which coincided with elevated levels of cell death. These findings identify BI-69A11 as a potent inhibitor of AKT that is capable of eliciting effective regression of xenograft melanoma tumors. [source] Correlation of Her-2/neu Gene Amplification with Other Prognostic and Predictive Factors in Female Breast CarcinomaTHE BREAST JOURNAL, Issue 4 2005Reshma Ariga MD Abstract: , The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p < 0.0003), ER (p = 0.0001) and PR (p < 0.0001) negative tumors, over-expression of MIB-1 (p < 0.0005) and high tumor grade (p = 0.0009), while size of the tumor (p = 0.08) and age of the patients (p = 0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification. [source] Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 miceBIOELECTROMAGNETICS, Issue 3 2007Thomas Tillmann Abstract The purpose of this study using a total of 1170 B6C3F1 mice was to detect and evaluate possible carcinogenic effects in mice exposed to radio-frequency-radiation (RFR) from Global System for Mobile Communication (GSM) and Digital Personal Communications System (DCS) handsets as emitted by handsets operating in the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a period of 2 years to three different whole-body averaged specific absorption rate (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the organ-related tumor incidence, pairwise Fisher's test did not show any significant increase in the incidence of any particular tumor type in the RF exposed groups as compared to the sham exposed group. Interestingly, while the incidences of hepatocellular carcinomas were similar in EMF and sham exposed groups, in both studies the incidences of liver adenomas in males decreased with increasing dose levels; the incidences in the high dose groups were statistically significantly different from those in the sham exposed groups. Comparison to published tumor rates in untreated mice revealed that the observed tumor rates were within the range of historical control data. In conclusion, the present study produced no evidence that the exposure of male and female B6C3F1 mice to wireless GSM and DCS radio frequency signals at a whole body absorption rate of up to 4.0 W/kg resulted in any adverse health effect or had any cumulative influence on the incidence or severity of neoplastic and non-neoplastic background lesions, and thus the study did not provide any evidence of RF possessing a carcinogenic potential. Bioelectromagnetics 28:173,187, 2007. © 2006 Wiley-Liss, Inc. [source] Semiparametric Bayes Multiple Testing: Applications to Tumor DataBIOMETRICS, Issue 2 2010Lianming Wang Summary In National Toxicology Program (NTP) studies, investigators want to assess whether a test agent is carcinogenic overall and specific to certain tumor types, while estimating the dose-response profiles. Because there are potentially correlations among the tumors, a joint inference is preferred to separate univariate analyses for each tumor type. In this regard, we propose a random effect logistic model with a matrix of coefficients representing log-odds ratios for the adjacent dose groups for tumors at different sites. We propose appropriate nonparametric priors for these coefficients to characterize the correlations and to allow borrowing of information across different dose groups and tumor types. Global and local hypotheses can be easily evaluated by summarizing the output of a single Monte Carlo Markov chain (MCMC). Two multiple testing procedures are applied for testing local hypotheses based on the posterior probabilities of local alternatives. Simulation studies are conducted and an NTP tumor data set is analyzed illustrating the proposed approach. [source] Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of CasesBRAIN PATHOLOGY, Issue 4 2008Kathreena M. Kurian Abstract Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities. We have used microarray comparative genomic hybridization to study a series of SE (n = 12). A whole-genome array at 0.97-Mb resolution showed copy number abnormalities in five of 12 cases (42%). Two cases (17%) showed regions of loss on chromosome 6. More detailed analysis of all cases using a chromosome 6 tile-path array confirmed the presence of overlapping regions of loss in only these two cases. One of these cases also showed trisomy chromosome 7. Monosomy of chromosome 8 was seen in a further two cases (17%), and a partial loss on chromosome 14 was observed in one additional case. This is the first array-based, genome-wide study of SE. The observation that five of 12 cases examined (42%) at 0.97-Mb resolution showed chromosomal copy number abnormalities is a novel finding in this tumor type. [source] Reduced Apoptosis Rates in Human SchwannomasBRAIN PATHOLOGY, Issue 1 2005Tamara Utermark Schwannomas, tumors originating from Schwann cells, represent a frequent neurological tumor and can occur both in a genetic disorder called neurofibromatosis type 2 (NF2) and sporadically. In both cases the genetic background is identical as all schwannomas are caused by biallelic mutations in the tumor suppressor gene NF2 coding for merlin. Mutations in this gene have also been found to be responsible for 50% to 60% of spontaneous and 100% of the NF2 associated meningiomas. The NF2 gene product, merlin, links transmembrane proteins to the cytoskeleton and is involved in intracellular signaling processes. It has previously been shown that reexpression of wild-type merlin in primary human schwannoma cells leads to an increase in the number of apoptotic cells. Here, we report in vivo and in vitro evidence that the basal apoptosis rate of primary human schwannoma cells is reduced in comparison to that of normal Schwann cells, supporting the idea that in this benign tumor type, apoptosis has a role in tumorigenesis. [source] Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compressionCANCER, Issue 15 2010Dirk Rades MD Abstract BACKGROUND: Based on an analysis of 1852 retrospectively evaluated patients with metastatic spinal cord compression (MSCC), a scoring system was developed to predict survival. This study was performed to validate the scoring system in a new data set. METHODS: The score included 6 prognostic factors: tumor type, interval between tumor diagnosis and MSCC, other bone or visceral metastases, ambulatory status, and duration of motor deficits. Scores ranged between 20 and 45 points, and patients were initially divided into 5 groups: those with 20 to 25 points, those with 26 to 30 points, those with 31 to 35 points, those with 36 to 40 points, and those with 41 to 45 points. To facilitate the clinical use of the score, the patients were regrouped into 3 groups: those with 20 to 30 points, those with 31 to 35 points, and those with 36 to 45 points. In this study, data of 439 new patients were included who were divided into the same prognostic groups as in the preceding study. RESULTS: In this study, the 6-month survival rates were 7% (for those with 20-25 points), 19% (for those with 26-30 points), 56% (for those with 31-35 points), 73% (for those with 36-40 points), and 90% (for those with 41-45 points), respectively (P < .0001). After regrouping, the 6-month survival rates were 14% (for those with 20-30 points), 56% (for those with 31-35 points), and 80% (for those with 36-45 points), respectively, in this study (P < .0001). CONCLUSIONS: In the current study, the difference in 6-month survival between the prognostic groups was found to be as significant as in the preceding study. Thus, this scoring system was considered valid to estimate survival of MSCC patients. The system could have been simplified by including only 3 instead of 5 prognostic groups. Cancer 2010. © 2010 American Cancer Society. [source] Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastasesCANCER, Issue 10 2007Dirk Rades MD Abstract BACKGROUND. The authors investigated whether stereotactic radiosurgery (SRS) alone improved outcomes for patients in recursive partitioning analysis (RPA) Classes 1 and 2 who had 1 to 3 brain metastases compared with whole-brain radiotherapy (WBRT). METHODS. Data regarding 186 patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases and who received either 30 to 40 grays (Gy) of WBRT (n = 91 patients) or 18 to 25 Gy SRS (n = 95 patients) were analyzed retrospectively. Eight other potential prognostic factors were evaluated regarding overall survival (OS), entire brain control (BC), local control (LC) of treated metastases, and brain control distant from treated metastases (distant control [DC]): Those 8 factors were age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to radiotherapy. RESULTS. On multivariate analysis of OS, age ( risk ratio [RR], 1.51; P = .024), Karnofsky performance status (KPS) (RR, 1.98; P = .002), and extracranial metastases (RR, 2.26; P < .001) were significant, whereas the radiation regimen was not significant (P = .89). On multivariate analysis of BC, only the radiation regimen (RR, 1.33; P = .003) was found to be significant. On multivariate analysis of LC, radiation regimen (RR, 1.63; P < .001) and sex (RR, 1.62; P = .022) were significant. On multivariate analysis of DC, KPS (RR, 1.85; P = .049) and extracranial metastases (RR, 1.69; P = .047) were significant. The radiation regimen was not found to be significant even on univariate analysis (P = .80). In RPA class subgroup analyses, BC and LC were better after SRS than WBRT for patients in RPA Classes 1 and 2, whereas OS and DC did not differ significantly. CONCLUSIONS. For patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases, SRS alone was associated with improved BC and LC compared with 30 to 40 Gy WBRT, whereas OS and DC were not significantly different. Similar results were observed in separate subgroup analyses of patients in RPA Class 1 and RPA Class 2. Cancer 2007. © 2007 American Cancer Society. [source] | |||||||||||||||||||||||||||||||||||||