Home About us Contact
|
Home About us Contact | ||
|
|
||
Malignant Cells (malignant + cell)
Terms modified by Malignant Cells Selected AbstractsInhibition of cell proliferation and glucose uptake in human laryngeal carcinoma cells by antisense oligonucleotides against glucose transporter-1HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2009Shui-Hong Zhou PhD Abstract Background. Malignant cells show increased glucose uptake in vitro and in vivo, which is thought to be mediated by glucose transporters. In this study, we investigated the effect of plasmid-derived antisense RNA against the Glut-l gene on proliferation and glucose uptake in laryngeal carcinoma Hep-2 cells. Methods. The expression plasmids pcDNA3.1(+)-Glut-1 and pcDNA3.1(+)-anti Glut-1 were constructed. The MTT method was used to assess cell growth inhibition. The expression of Glut-1 mRNA and protein was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Results. After transfection, Glut-1 AS clearly inhibited glucose uptake and cell growth in Hep-2 cells, and we observed a decrease in the expression of Glut-1 mRNA and protein in Hep-2 cells. Conclusions. Glut-1 AS decreases glucose uptake and inhibits the proliferation of Hep-2 cells. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] The therapeutic potential of the proteasome in leukaemia,HEMATOLOGICAL ONCOLOGY, Issue 2 2008Scott Marshall McCloskey Abstract Many cellular processes converge on the proteasome, and its key regulatory role is increasingly being recognized. Proteasome inhibition allows the manipulation of many cellular pathways including apoptotic and cell cycle mechanisms. The proteasome inhibitor bortezomib has enhanced responses in newly diagnosed patients with myeloma and provides a new line of therapy in relapsed and refractory patients. Malignant cells are more sensitive to proteasome inhibition than normal haematopoietic cells. Proteasome inhibition enhances many conventional therapies and its role in leukaemia is promising. Copyright © 2008 John Wiley & Sons, Ltd. [source] Colon cancer cell adhesion in response to Src kinase activation and actin-cytoskeleton by non-laminar shear stress,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Vijayalakshmi Thamilselvan Abstract Malignant cells shed from tumors during surgical resection or spontaneous metastasis experience physical forces such as shear stress and turbulence within the peritoneal cavity during irrigation, laparoscopic air insufflation, or surgical manipulation, and within the venous or lymphatic system. Since physical forces can activate intracellular signals that modulate the biology of various cell types in vitro, we hypothesized that shear stress and turbulence might increase colon cancer cell adhesion to extracellular matrix, potentiating metastatic implantation. Primary human malignant colon cancer cells isolated from resected tumors and SW620 were subjected to shear stress and turbulence by stirring cells in suspension at 600 rpm for 10 min. Shear stress for 10 min increased subsequent SW620 colon cancer cell adhesion by 40.0,±,3.0% (n,=,3; P,<,0.001) and primary cancer cells by 41.0,±,3.0% to collagen I when compared to control cells. In vitro kinase assay (1.5,±,0.13 fold) and Western analysis (1.34,±,0.04 fold) demonstrated a significant increase in Src kinase activity in cells exposed shear stress. Src kinase inhibitors PP1 (0.1 µM), PP2 (20 µM), and actin-cytoskeleton stabilizer phalloidin (10 µM) prevented the shear stress stimulated cell adhesion to collagen I. Furthermore, PP2 inhibited basal (50.0,±,2.8%) and prevented shear stress induced src activation but phalloidin pretreatment did not. These results raise the possibility that shear stress and turbulence may stimulate the adhesion of malignant cells shed from colon cancers by a mechanism that requires both actin-cytoskeletal reorganization an independent physical force activation of Src kinase. Blocking this pathway might reduce tumor metastasis during surgical resection. Published 2004 Wiley-Liss, Inc. [source] Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2010Shinichi Ohba J Oral Pathol Med (2010) 39: 74,78 Object:, Malignant cells show increased uptake, which is considered to be facilitated by glucose transporters (GLUTs). Increased GLUT-1 expression has been reported in many human cancers. We hypothesized that a oral squamous cell carcinoma, characterized by high frequency of lymph node metastasis, distant metastasis or local recurrences, was associated with GLUT-1 overexpression in invasion front. Methods:, GLUT-1 immunostaining in invasion front was studied on 24 oral squamous cell carcinomas, and revealed the correlation with the clinical characteristics. Result:, The analysis showed that all oral squamous cell carcinoma patients and GLUT-1 expression correlated the depth of the tumors (P = 0.023 < 0.05). Furthermore the survival of patients who had overexpression of invasion front was significant shorter than that of patients with GLUT-1 weakly positive (P = 0.046 < 0.05). No significant association was noted between GLUT-1 immunostaining and either age, gender, subsites, tumor size, or lymph node status. Conclusion:, The present study shows that GLUT-1 served as a marker indicating that tumors with deep invasion tended to result in a worse prognosis in patients due to either lymph node metastasis, a recurrence of the primary lesion or distant metastasis. [source] The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2004A. Kerber Summary Background :,Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. Aim :,To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. Methods :,We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. Results :,Receiver,operator curve analysis revealed <0.7 ,g/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). Conclusion :,The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice. [source] CSF cytology has limited value in the evaluation of patients with ependymoma who have MRI evidence of metastasis,PEDIATRIC BLOOD & CANCER, Issue 2 2006Igor M. Poltinnikov MD Abstract Purpose To investigate the usefulness of cerebrospinal fluid (CSF) cytology in pediatric patients with ependymoma who relapsed after focal irradiation. Methods Eighty-eight patients with ependymoma received conformal radiotherapy (CRT) from July 1997 through January 2003 on an IRB approved prospective treatment protocol. CSF cytology results from evaluations performed prior to CRT and at the time of failure were reviewed for patients who progressed after CRT as documented by magnetic resonance imaging (MRI). Results Twenty-two patients had MRI documented evidence of progression after CRT. Ten patients developed distant failure without local failure, four had combined local and distant failure and eight had local failure without distant failure. The median time from the start of CRT to progression was 19 months (range: 6,73). CSF cytology at diagnosis was negative for the presence of malignant cells in all patients. At the time of progression, CSF cytology was performed in 16 of 22 patients including all 10 patients with distant failure without local recurrence. Malignant cells were not found in any of the evaluated CSF specimens including those with distant failure documented by MRI. Conclusions CSF cytology does not add valuable information when evaluating patients with ependymoma who have evidence of distant failure documented by MRI. The usefulness of CSF cytology in the general follow-up evaluation of pediatric patients with ependymoma remains uncertain. © 2005 Wiley-Liss, Inc. [source] Pilot study: rapamycin in advanced hepatocellular carcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010M. Schöniger-Hekele Summary Background, The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Aim, To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC). Methods, Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study. Results, Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver-Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months. Conclusion, Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective. [source] Peripheral nervous system involvement as presenting symptom of systemic B-cell lymphomaJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004C Casellato Peripheral nervous system involvement has been reported in systemic B or T cell lymphoma and may result from intraneural localization of lymphoma resulting in meningo-radiculopathy or mononeuropathies, or manifest as a sensory-motor polyneuropathy sometimes mimicking chronic inflammatory demyelinating polyneuropathy. We report two patients with a previously unknown NHL presenting in both with a stepwise progressive asymmetric multiradiculoneuropathy initially misdiagnosed as inflammatory radiculopathy. A 58-year-old man presented with a 2 year history of stepwise progressive peroneal sensory loss, impotence, and lower limb painful asymmetric neuropathy. Lumbosacral MRI was normal. Electrophysiological studies were consistent with an axonal multiradiculoneuropathy while CSF examinations repeatedly showed increased protein levels (80,91 mg/dl) with slightly increased white cells (<10 mm3) but no malignant cell. The patient repeatedly failed to respond to steroids although he consistently deteriorated at their suspension. An MRI performed 2 years later when multiple cranial nerve palsies appeared showed bilateral T1 and T2 hyperintensities in the brain and cervical spinal cord. An extensive investigation for neoplasm was negative. The patient died from an intracranial hemorrhage during anticoagulant therapy for deep vein thrombosis. Autoptic studies revealed a widespread non-Hodgkin's type B lymphoma with massive systemic and neural involvement including cauda equina and spinal cord. A 54-year-old man presented with a 1 year history of impotence, urinary incontinence, progressive asymmetric painful distal sensorimotor impairment at four limbs and prominent weight loss. Four previous CSF examinations revealed increased protein levels (80,100 mg/dl), and slightly but inconsistently increased white cells (1,11/mm3) but no malinant cells. Steroids were repeatedly ineffective although the patient consistently deteriorated whenever steroids were discontinued. On admission electrophysiological studies showed an axonal asymmetric polyradiculoneuropathy. Brain and spinal MRI was normal while bone marrow biopsy and aspiration disclosed a B cell lymphoma. [source] Uveal melanoma and macular degeneration: molecular biology and potential therapeutic applicationsACTA OPHTHALMOLOGICA, Issue 8 2008Mario-Alexander Economou Abstract. Uveal melanoma is the most common primary intraocular malignant tumor in adults with 30% to 50% of patients that ultimately succumb to metastatic disease, mainly to the liver. (Shields et al. 1991) Although new diagnostic and therapeutic tools have been developed during the most recent years, only the eye conservation rate has been achieved, while the survival rate remains poor. The reason for this liver-homing is largely unknown, but it is conceivable that hepatic environmental factors may be implicated in the growth, dissemination, and progression of this malignancy. The insulin-like growth factor (IGF-1) that binds to the IGF-1 receptor (IGF-1R) is mainly produced in the liver. It has been shown to be crucial for tumor transformation, maintenance of malignant phenotype, promotion of cell growth, and prevention of apoptosis. (Baserga 1995) The hepatocyte growth factor/scatter factor (HGF/SF) is another growth factor produced in the liver and exerts its biological effects through binding to the plasma membrane receptor c-Met. The activation of this receptor by HGF/SF ligand can induce proliferation, motility, adhesion, and invasion of tumor cells. (Cruz et al. 2003) Metastasis is a process involving many components, including tumor cell adhesion, migration, extracellular matrix (ECM) proteolysis, and invasion. The tumor cells undergo intravasation, disperse via the vascular and the lymphatic systems, and finally extravasate to invade the secondary sites. In all these steps, proteolytic enzyme systems are involved, including the matrix metalloproteinase (MMP) system and the plasminogen activation system. The migration of a malignant cell through the ECM and the basement membrane requires proteolytic activities. (Stetler-Stevenson et al. 1993). Efforts to target the IGF-I system has been made with different types of cancer but not with uveal melanoma. [source] Mesothelioma Symposium 11.30,12.30 Tuesday 16 September 2003CYTOPATHOLOGY, Issue 2003Darrel Whitaker Dr The diagnosis of malignant mesothelioma on the cytology of serous effusions is a two-phase process. First is to determine that the effusion is malignant based on morphological features such as a highly cellular fluid with many large three dimensional cell aggregates, and/or the recognition of minor malignant criteria including prominent cell engulfment, uniformly present very prominent nucleoli, or the finding of very large (giant) cells. In cell block sections, strong positive staining with EMA often with cell membrane accentuation provides compelling support for a cytological diagnosis of malignancy. Second is to recognize that the malignant cells have a mesothelial phenotype and do not represent metastatic malignancy (usually adenocarcinoma). Criteria in support of mesothelioma include the lack of a ,two cell' population, that is one native (mesothelial) and one foreign (metastatic), cells with abundant dense staining cytoplasm, the presence of ,windows' where mesothelioma cells lie in close apposition and intracytoplasmic glycogen presenting either as small peripheral vacuoles on MGG stained smears or large yellow refractile crescents on Papanicolaou stained smears. In addition, mesothliomas often possess connective tissue stromal cores occurring as either well-formed collagen within papillary aggregates or lying free as pink (MGG) or light green (Pap) amorphous material in the background of the smear or in loose association with mesothelioma cells. Finally small orange staining squamous-like cells can occasionally be identified and sometimes this may be a very prominent finding and has resulted in the false impression of a squamous cell carcinoma. Almost certainly these cells represent apoptotic tumour cells. The connective tissue mucin hyaluronic acid may be found as a net-like pattern in the smear background or as large hard-edged magenta-stained vacuoles on MGG-stained smears. Cell block sections provide architectural information and it is usually possible to separate mesothelioma aggregates with their cuboidal cells, central nuclei and abundant dense cytoplasm arranged in solid, papillary or hollow clusters from those of adenocarcinoma with less dense, often foamy cytoplasm, often composed of columnar cells with elongated nuclei. Aggregate form in adenocarcinoma can be variable but true acini are a rare finding. These cell block sections provide an ideal medium for histochemistry (PAS with and without diastase digestion) and immunocytochemistry. By using a panel of antibodies (Calretinin and CK 5/6, BerEp4, CEA, B72.3) it is almost always possible to distinguish mesothelioma from metastatic adenocarcinoma. Calretinin and CK 5/6 positive staining and absent staining with BerEp4, CEA and B72.3 is considered diagnostic of mesothelioma. [source] The utility of transbronchial (Wang) fine needle aspiration in lung cancer diagnosisCYTOPATHOLOGY, Issue 1 2001M. T. Siddiqui The utility of transbronchial (Wang) fine needle aspiration in lung cancer diagnosis We evaluated our experience with transbronchial fine needle aspiration (TBNA) in cancer diagnosis over a period of 1 year. A total of 51 aspirates were performed by specialist chest physicians in the presence of a cytopathologist who made on spot evaluation of Diff-Quik smears for adequacy and guided the aspirator for additional sampling if necessary. Two clusters of at least 10 malignant cells were required on the Diff-Quik smears to render an on the spot positive diagnosis of malignancy. Aspirates showing atypical cells or few malignant cells not fulfilling the above criteria were placed in a suspicious category and additional material was requested. The TBNA results were correlated with the transbronchial biopsy when available. [source] Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typingDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2009Roberto G. Gamez M.D. Abstract Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47-year-old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell-in-cell arrangements, and short rows of cells with intervening "windows," all features reminiscent of mesothelial cells. No keratinization or three-dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber-EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Role of computerized morphometric analysis in diagnosis of effusion specimensDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2006B. Arora M.D. Abstract The present study was undertaken to compare morphometric analysis of cells in 100 effusion samples, with unaided cytological diagnosis. All the cases in the form of Leishman's stained smears were subjected to computerized-interactive morphometry (CIM) by usage of Image analysis software. On routine cytological examination, 44 cases were benign, 26 were malignant, and 30 cases were placed in "atypical" category. On morphometry, values for mean nuclear area (MNA) and mean cytoplasmic area (MCA) in benign cases were found to be 58.39 ± 12.22 ,m2 and 185.70 ± 43.69 ,m2, while for malignant cases were 120.12 ± 16.28 ,m2 and 274.65 ± 61.01 ,m2, respectively (P < 0.001, P < 0.001, highly significant). Significant differences were also noted among benign, atypical, and malignant cases for MNA (P < 0.001). The differences between atypical and malignant cases for N/C (nuclear/cytoplasmic) ratio were also found to be statistically significant (P < 0.001). Finally, 46 cases were found to be benign, 39 malignant, and 15 in the category of atypical cases. CIM helps in better and quicker sorting for malignant cells. MNA and N/C ratio are the most significant parameters in differentiating various cells in effusions. MCA constitutes as another useful parameter. Salient features of CIM, including their applications in the light of current study, are discussed. Diagn. Cytopathol. 2006;34:670,675. © 2006 Wiley-Liss, Inc. [source] Detection of tumor cells in body cavity fluids by flow cytometric and immunocytochemical analysisDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2006Awtar Krishan Ph.D. Abstract Measurement of electronic volume versus DNA content of nuclei can be used to discriminate between normal and malignant cells. Epithelial membrane antigen immunocytochemistry (EMA-ICC), a helpful ancillary test in body cavity fluids, is not universally accurate for detecting malignancy in effusions. The current study was undertaken to determine if multiparametric flow cytometry (based on simultaneous analysis of light scatter, nuclear volume, DNA, and nuclear protein content) in combination with (EMA-ICC) could be used for the detection of malignant cells in peritoneal and pleural fluids. We studied 130 body cavity fluids (68 peritoneal and 62 pleural fluids) by conventional cytology and multiparametric laser flow cytometry. EMA-ICC was performed using EMA antibodies and L-SAB detection system (DakoCytomation, Carpinteria, CA). EMA-ICC had significantly higher sensitivity than conventional cytology (79% versus 59%, P = 0.016) and ploidy (79% versus 38%, P = 0.001). Cytology had significantly higher specificity than ploidy (97% versus 82%, P = 0.012). The differences in specificity between EMA-ICC and ploidy (87% versus 82%, P= 0.607) or EMA-ICC and cytology (87% versus 97%, P = 0.109) were not statistically significant. However, assuming serial testing, sensitivity increased significantly for the combinations of cytology and EMA-ICC (79.4%, P = 0.016) and cytology and ploidy (73.5%, P = 0.004) as compared to cytology alone (58.8%). Also, the combination of cytology and ploidy had a higher sensitivity than ploidy alone (73% versus 38%, P < 0.0001). However, the sensitivity associated with the three tests used in serial (85.3%) was not significantly different from the sensitivities corresponding to the combination of cytology and EMA-ICC (79%) or cytology and ploidy (73%). Multiparametric flow cytometry utilizing high resolution DNA, nuclear volume, protein measurement, and ICC, in combination with cytomorphology, may be a valuable tool for rapid identification of malignant cells in body cavity fluids. Diagn. Cytopathol. 2006;34:528,541. © 2006 Wiley-Liss, Inc. [source] Exfoliative sputum cytology of cancers metastatic to the lung,DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Tehmina Z. Ali M.D. Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source] Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy materialDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2004Michael F. Weiner M.D. Abstract The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT-1), a facilitative cell surface glucose transport protein, is aberrantly expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the expression of GLUT-1 by immunochemistry on FNAB material to determine its value in distinguishing cystic SCC from BCSL of the head and neck. A 5-yr retrospective review of all head and neck cystic squamous lesions having FNAB specimens with cell block material, radiological studies, and histological confirmation was performed at our institution. Cell block material from 24 cystic squamous lesions, including 8 (33%) BCSL (7 branchial cleft cysts and 1 thyroglossal duct cyst[TDC]) and 16 (67%) metastatic SCCs with cystic/liquefactive degeneration, was retrieved and immunostained with anti-GLUT-1. GLUT-1 expression was considered positive when at least 10% of squamous cells exhibited distinct cell membrane reactivity. Positive GLUT-1 immunostaining was detected in all 16 SCCs and in none of the 8 BCSLs. In the carcinoma cases, the majority of malignant cells exhibited GLUT-1 reactivity; only a minor population of well-differentiated SCC cells displaying keratinization and arranged as squamous pearls did not express GLUT-1. GLUT-1 expression in cell block material can help to distinguish cystic SCCs from BCSLs of the head and neck. In conjunction with clinical and radiological correlation, GLUT-1 immunoreactivity can be an important diagnostic aid when the cytological findings are ambiguous. Diagn. Cytopathol. 2004;31:294,299. © 2004 Wiley-Liss, Inc. [source] Airborne fungal spores, pollen grains, and vegetable cells in routine Papanicolaou smearsDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2004Ph.D., Rafael Martínez-Girón M.D. Abstract The objective was to demonstrate the presence of airborne fungal spores, pollen grains, and vegetable cells in smears and establish their significance. Microscopic examination was of smears stained by the Papanicolaou technique. We found several types of airborne spores (Alternaria, Exserohilum, Aspergillus, Cladosporium, Epicoccum, Curvularia, and Ascosmycete), pollen grains (Lilium, bullrush, Pinus, Acacia, hazelnut, and oak), and several types of vegetable cells. The existence of these structures may be due to intrinsic or to extrinsic contamination of the sample. Anemophilous fungi spores and pollen grains have been shown to possess great allergenic capacity. Pollen grains and vegetable cells may be mistaken for certain microorganisms or malignant cells. Diagn. Cytopathol. 2004;30:381,385. © 2004 Wiley-Liss, Inc. [source] Cervicovaginal (Papanicolaou) smear findings in patients with malignant mixed Müllerian tumorsDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2003Mary B. Casey M.D. Abstract Malignant mixed Müllerian tumor is a rare neoplasm that occurs most frequently in elderly patients. It is characterized by a mixture of malignant epithelial and sarcomatous components. Little has been published about Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors. We present our experience, with an emphasis on cytologic detail. Nine patients (median age, 65 yr) met our study criteria. All available smears and surgical specimens were reviewed. Four smears were positive for malignancy, with a sensitivity of 44% (3 adenocarcinoma, and 1 squamous-cell carcinoma, small-cell type). The results of our study showed that Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors are seen in patients with advanced-stage disease with involvement of the lower uterine segment or cervix. The usual finding is large numbers of high-grade epithelial malignant cells in a necrotic background. The mesenchymal component rarely sheds cells visible on Papanicolaou smear. Diagn. Cytopathol. 2003;28:245,249. © 2003 Wiley-Liss, Inc. [source] Follicular variant of papillary carcinoma: Cytologic findings on FNAB samples,experience with 16 casesDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2001Franco Fulciniti M.D. Abstract Between January 1, 1992 and December 31, 1997, a cytopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPC) was made on a series of 16 out of 18 patients with palpable nodules who underwent fine-needle aspiration biopsy (FNAB) in our Department. The results of aspiration biopsy were followed by histopathological examination of the surgically excised tissues. There were three false-negative aspirations (16.6%), of which two were probably bound to fine-needle sampling and one due to a mixture of benign and malignant cells which had originally gone unrecognized. The accuracy of the cytopathologic diagnosis in this variant was 88.8%. An analysis of the diagnostic cytopathological criteria was performed, which demonstrated the importance of both architectural features (monolayered and branching sheets, microacinar structures, and their combinations) and nuclear features (presence of nuclear grooves). Background -bound features were mainly represented by dense, nonfilamentous colloid. The cytopathologic findings in FVPC were compared to those found in a series of 10 usual papillary carcinomas (UPC) and 10 follicular neoplasms (FN). These latter had originally been diagnosed by FNAB and were subsequently classified histologically as follicular adenoma (n = 6), follicular carcinoma (n = 3), or adenomatoid colloid nodule (n = 1). Statistical evaluation was performed on the cytopathological findings in the three classes of lesions (FVPC, UPC, and FN) as to their presence and relative frequency or absence by using a nonparametric one-way ANOVA (Kruskall-Wallis) and, where necessary, a Mann-Whitney U test. Papillary cellular fragments and multinucleated giant cells (P < 0.005), nonfilamentous dense colloid, squamoid cells, and syncytia were significantly more represented in UPC than in FVPC (P < 0.05), while histiocytes were significantly more frequent in FVPC (P < 0.005). Other nuclear and/or background features were significant only in the distinction between papillary carcinomas as a group and FN. The cytological differential diagnosis of the FVPC is briefly discussed with relevance to the possible pitfalls caused by its peculiar cyto- and histomorphology. Diagn. Cytopathol. 2001;25:86,93. © 2001 Wiley-Liss, Inc. [source] Extensive flow cytometric characterization of plasmacytoid dendritic cell leukemia cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Laszlo Gopcsa Abstract:,Objectives:,Accumulating evidence suggests that non-T, non-B cell CD4+CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. Methods:,In this work we present the immunophenotypic and genotypic features of bone marrow (BM), peripheral blood (PB), lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, BM, PB, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation, and co-stimulatory molecules were used. Results and conclusion:,The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2, and granzyme-B corresponding to the preplasmacytoid dendritic cell developmental stage. The presence of CD11a/CD18, CD84, CD91, CD95, ,v,5, CDw197, and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells. Completing the immunophenotypes with multidrug resistance function can provide additional information for characterizing pDC leukemia. [source] Expression of DNA repair gene Ku80 in lymphoid neoplasmEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005Tsai-Yun Chen Abstract:,Objectives:,Ku, a heterodimer of KU70 and Ku80 that binds to double-strand DNA breaks (DSBs) and activates the catalytic subunit (DNA-PKcs) when DNA is bound, is essential in DSB repair and V(D)J recombination. Ku80 is a putative tumor suppressor gene that might play an important role in drug resistance. Our aim was to determine the role of Ku80 in lymphoid malignancy. Patients and methods:,Competitive reverse transcription-polymerase chain reaction assays were performed and the expression levels of Ku80 were measured in normal peripheral blood mononuclear cells (n = 9) and malignant cells from 25 patients with acute lymphoblastic leukemia (ALL) (14 children, 11 adults), and chronic lymphoproliferative disorders (n = 6). The Ku80 transcripts were sequencing for the possibility of mutation. Results:,No mutation or Ku80 variant at the RNA level was seen in any patient samples or in the Raji or CCRF-CEM cell lines. In Ku80 expression, 8.8-, 1.9-, and 6.2-fold mean increases were seen in adult, pediatric ALL, and chronic lymphoid malignancies compared with the control. The Ku80 was significantly higher in adult than in pediatric ALL (P = 0.02). The amount of Ku80 expression in ALL was moderately correlated with peripheral white blood cell counts, but not with Ki67 labeling index. High Ku80 expressers (higher than the mean of all patients with ALL) tended to respond poorly to therapy: Only 22% of high Ku80 expressers achieved durable complete remission compared to 62% of low expressers. Conclusions:,Our study suggests that Ku80 might contribute to generally poor prognoses in adult ALL. [source] The antiapoptotic effects of blood constituents in patients with chronic lymphocytic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Yonit Bomstein Abstract: Objective: Clonal B-lymphocytes of chronic lymphocytic leukemia (B-CLL) are characterized by decreased sensitivity to programmed cell death and, therefore, they accumulate in vivo. However, these malignant cells die rapidly in vitro. In the current study we concentrated on the contribution of autologous serum (AS) and lymphocyte subsets to the survival of the malignant cells in vitro. Methods: Mononuclear cells from the peripheral blood of 26 CLL patients and 24 controls were incubated overnight in the presence or absence of AS and heat-inactivated AS (HI-AS) or fetal calf serum (FCS). Also, isolated B cells were incubated at different concentrations in the presence of AS and/or isolated T cells. The level of apoptosis of CD19+ cells was measured by flow cytometry. Results: Spontaneous apoptosis of unfractionated B-CLL cells incubated with AS, FCS or without serum was significantly lower than the rate of B-cell death in the control group, in similar culture conditions. AS had an antiapoptotic effect on unfractionated B-CLL cells when compared with FCS. The rate of apoptosis of B-CLL cells was directly associated with stage. HI of AS had a variable effect, which was related to the stage of the disease. High concentrations of B cells and the addition of autologous T cells reduced the rate of apoptosis when incubated without serum. The antiapoptotic effect of T cells was most prominent in progressive stages. Conclusions: B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression. [source] Oral lichen planus has a high rate of TP53 mutations.EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2002A study of oral mucosa in Iceland Oral squamous cell carcinoma (OSCC) is a world-wide health problem. In addition to external exposure (smoking and alcohol), certain oral lesions may increase the risk of oral cancer (e.g. leukoplakia, erythroplakia, and oral lichen planus). TP53 has been implicated in OSCC, but there are limited studies of mutations in premalignant oral lesions. In this study, 55 samples from OSCC, 47 from hyperkeratotic (HK) oral mucosa, clinically diagnosed as white patches, 48 samples from oral lichen planus (OLP), and 12 biopsies from normal oral mucosa were studied immunohistochemically for expression of TP53 protein. From all the carcinoma samples and selected non-malignant samples showing moderate or strong TP53 protein expression, malignant cells or TP53-positive nuclei were microdissected and screened for mutations in exons 5,8 by constant denaturation gel electrophoresis. Moderate to strong TP53 protein staining was seen in 56% of OSCC, 32% of OLP but only in 13% of HK. All OLP samples showed a characteristic pattern of positive nuclei confined to the basal layer, whereas TP53 staining was seen in suprabasal nuclei in HK. Mutation rate was 11 out of 52 for OSCC, three out of 20 tested for HK and, remarkably, nine out 27 tested for OLP. There was no correlation between TP53 protein staining and TP53 mutations. No associations were found with anatomical sites or disease progression. The unexpectedly high mutation rate of OLP might explain the premalignant potential of this lesion. [source] Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanomaEXPERIMENTAL DERMATOLOGY, Issue 6 2003Heike Rothfels Abstract:, Selective killing of tumors can be achieved by targeting the transcription of suicide genes via specific DNA control elements to malignant cells. Three different enhancer-promoter systems were constructed and evaluated for their capability to direct gene expression to melanoma. Two tissue-specific (tyrosinase and MIA) promoters and one weak viral promoter were fused to multiple tandem copies of a melanocyte-specific enhancer element. Reporter gene assays revealed a maximum increase in transcription by combining each promoter with 3,4 copies of the enhancer and demonstrated that all enhancer-promoter combinations exhibited tissue-specific activity. Though this activity was still significantly less than that of the strong but unspecific cytomegalo virus (CMV) promoter. In contrast, when these combinations were employed to drive the expression of two suicide genes, encoding the diphtheria toxin A chain (DT-A) and the prodrug-activating herpes simplex virus thymidine kinase (TK), respectively, only those constructs in which transcription was under the control of tissue-specific promoter elements mediated selective killing of melanoma cells. This killing was in the range of cell death induced by CMV promoter activity. Our data indicate that the enhancer/tyrosinase and enhancer/MIA promoter constructs but not the viral promoter constructs can provide a valuable tool for selective suicide gene expression in melanoma. [source] IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progressionEXPERIMENTAL DERMATOLOGY, Issue 4 2000K. Asadullah Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells. [source] Functional association of human Ki-1/57 with pre-mRNA splicing eventsFEBS JOURNAL, Issue 14 2009Gustavo C. Bressan The cytoplasmic and nuclear protein Ki-1/57 was first identified in malignant cells from Hodgkin's lymphoma. Despite studies showing its phosphorylation, arginine methylation, and interaction with several regulatory proteins, the functional role of Ki-1/57 in human cells remains to be determined. Here, we investigated the relationship of Ki-1/57 with RNA functions. Through immunoprecipitation assays, we verified the association of Ki-1/57 with the endogenous splicing proteins hnRNPQ and SFRS9 in HeLa cell extracts. We also found that recombinant Ki-1/57 was able to bind to a poly-U RNA probe in electrophoretic mobility shift assays. In a classic splicing test, we showed that Ki-1/57 can modify the splicing site selection of the adenoviral E1A minigene in a dose-dependent manner. Further confocal and fluorescence microscopy analysis revealed the localization of enhanced green fluorescent protein,Ki-1/57 to nuclear bodies involved in RNA processing and or small nuclear ribonucleoprotein assembly, depending on the cellular methylation status and its N-terminal region. In summary, our findings suggest that Ki-1/57 is probably involved in cellular events related to RNA functions, such as pre-mRNA splicing. Structured digital abstract ,,MINT-7041074: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with SF2P32 (uniprotkb:Q07021) by two hybrid (MI:0018) ,,MINT-7041232: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with SFRS9 (uniprotkb:Q13242) by pull down (MI:0096) ,,MINT-7041203: P80-Coilin (uniprotkb:P38432) and Ki-1/57 (uniprotkb:Q5JVS0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7041217: SMN (uniprotkb:Q16637) and Ki-1/57 (uniprotkb:Q5JVS0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7041189: SC-35 (uniprotkb:Q01130) and Ki-1/57 (uniprotkb:Q5JVS0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7041169: NPM (uniprotkb:P06748) and Ki-1/57 (uniprotkb:Q5JVS0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7041249: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with SFRS9 (uniprotkb:O60506) by pull down (MI:0096) ,,MINT-7041065: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with SFRS9 (uniprotkb:Q13242) by two hybrid (MI:0018) ,,MINT-7041069: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with YB1 (uniprotkb:P67809) by two hybrid (MI:0018) ,,MINT-7041079: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0915) with HNRPQ (uniprotkb:O60506) by two hybrid (MI:0018) ,,MINT-7041087: Ki-1/57 (uniprotkb:Q5JVS0) physically interacts (MI:0218) with HNRPQ3 (uniprotkb:O60506-1), HNRPQ2 (uniprotkb:O60506-2) and HNRPQ-1 (uniprotkb:O60506-3) by anti bait coimmunoprecipitation (MI:0006) [source] Expression and mutational analysis of MET in human solid cancersGENES, CHROMOSOMES AND CANCER, Issue 12 2008Patrick C. Ma MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker. © 2008 Wiley-Liss, Inc. [source] DNA repair pathways involved in anaphase bridge formationGENES, CHROMOSOMES AND CANCER, Issue 6 2007Ceyda Acilan Cancer cells frequently exhibit gross chromosomal alterations such as translocations, deletions, or gene amplifications an important source of chromosomal instability in malignant cells. One of the better-documented examples is the formation of anaphase bridges,chromosomes pulled in opposite directions by the spindle apparatus. Anaphase bridges are associated with DNA double strand breaks (DSBs). While the majority of DSBs are repaired correctly, to restore the original chromosome structure, incorrect fusion events also occur leading to bridging. To identify the cellular repair pathways used to form these aberrant structures, we tested a requirement for either of the two major DSB repair pathways in mammalian cells: homologous recombination (HR) and nonhomologous end joining (NHEJ). Our observations show that neither pathway is essential, but NHEJ helps prevent bridges. When NHEJ is compromised, the cell appears to use HR to repair the break, resulting in increased anaphase bridge formation. Moreover, intrinsic NHEJ activity of different cell lines appears to have a positive trend with induction of bridges from DNA damage. © 2007 Wiley-Liss, Inc. [source] Insertion of MLL sequences into chromosome band 5q31 results in an MLL-AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2003Ramona Deveney MLL gene rearrangements leading to production of MLL fusion proteins are commonly detected in infant leukemia patients; the most common MLL fusion associated with infant leukemia is the MLL-AF4 fusion. A single case of chromosomal rearrangement leading to production of an MLL fusion with AF5Q31, a gene structurally similar to AF4, has been detected recently in the malignant cells of an infant leukemia patient. We have identified a second case of MLL-AF5Q31 fusion, arising from an insertion of MLL sequences into chromosome 5, also in an infant leukemia patient. Because MLL and AF5Q31 are transcribed in opposite orientations, a simple balanced chromosomal translocation cannot produce a fusion protein, and complex chromosomal rearrangements such as insertions and inversions are required to produce an MLL-AF5Q31 fusion protein. This report demonstrates that chromosomal insertion of MLL sequences is a rare but recurrent abnormality associated with infant leukemia. © 2003 Wiley-Liss, Inc. [source] In vivo real-time diagnosis of nasopharyngeal carcinoma in situ by contact rhinoscopyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2005Martin Wai Pak FRCSEd(ORL) Abstract Background. Nasopharyngeal dysplasia or nasopharyngeal carcinoma in situ (NPCIS) lesions have rarely been reported. Timely diagnosis of the preinvasive lesion may improve prognosis. Contact endoscopy has been documented to accurately differentiate normal cells of the nasopharynx from malignant cells and allows a real-time diagnosis of primary and recurrent nasopharyngeal carcinoma (NPC) in a clinical setting. However, the role of contact endoscopy in the diagnosis of NPCIS is unknown. Methods. The superficial cells of the nasopharynx in a patient with NPCIS were examined in vivo under local anaesthesia by use of a contact rhinoscope. The contact endoscopic findings were correlated with the histologic findings of the biopsy. Results. The atypical cells of the lesion were magnified and visualized under contact endoscopy. Histopathologic analysis of the biopsied tissue confirmed the presence of NPCIS staining positively for Epstein-Barr virus (EBV),encoded RNA (EBER). No cell-free EBV DNA was detected in the sera of the patient. Conclusions. Contact endoscopy can accurately identify the atypical cells of a tiny preinvasive lesion in the nasopharynx in a clinical setting, which may not be evident in routine imaging examination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] | |||||||||||||||||||||||||||||||||||||||||||