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I Dardick

Publications and source records attributed to I Dardick.

At least 19 recordsLinked to original sources

Squamous cell carcinomas of the head and neck cultured in floating collagen gels: 1. The maintenance of stromal and epithelial elements in vitro without fibroblast overgrowth.

The study of the molecular biology of head and neck squamous cell carcinomas has been heavily reliant on the analysis of cell lines. This is largely because the maintenance of primary cell cultures is difficult. However, being monoclonal, cell lines are not representative of the primary tumor because of the loss of tumor cell heterogeneity. We report a technique for primary culture of squamous cell carcinomas with maintenance of epithelial and stromal cell components without overgrowth of the fibroblast cells. Phenotypic markers for fibroblasts and squamous cells were present up to 45 days after initiation of culture, and expression of epidermal growth factor receptor and involucrin in cultures paralleled that in the primary tumor. In vivo, tumor stromal elements are thought to play an important role in the support of epithelial cell growth. In the collagen gel system the preservation of the stromal cell component likely improves culture viability and growth. More importantly, this culture system allows the in vitro tumor to more accurately reflect the tumor from which it was derived, and it permits the study of primary squamous cell carcinomas under in vitro conditions.

Antibodies, Monoclonal

Quantitation and localization of cycling tumor cells in pleomorphic adenomas and myoepitheliomas: an immunohistochemical analysis.

Previous investigations have suggested that in certain salivary gland tumors only nonluminal (myoepithelial-like) tumor cells proliferate and that this may have histogenetic implications; however, no quantitative assessment of the cycling component is available. We decided, therefore, to enumerate the cycling luminal and nonluminal cells in 15 pleomorphic adenomas and six myoepitheliomas by using an antibody to proliferating cell nuclear antigen. The mean percentages of cycling luminal and nonluminal cells in pleomorphic adenomas were 2.3 +/- 1.4 and 2.4 +/- 2.3, respectively, and 2.1 +/- 0.7 of the tumor cells in myoepitheliomas. Even though duct-like structures in pleomorphic adenomas are considerably separated by more numerous nonluminal cells and, therefore, cycling cells may seem fewer, both cell types proliferate at similar rates. The results indicate that nonluminal cells are not the sole proliferative component in salivary gland tumors.

3,3'-Diaminobenzidine

Noninvasive and minimally invasive carcinoma ex mixed tumor: a clinicopathologic and ploidy study of 12 patients with major salivary tumors of low (or no?) malignant potential.

We studied 12 histologically malignant salivary tumors that showed complete encapsulation or only limited microscopic invasion. Most cases were histologically characterized by atypical and mitotically active luminal cells forming dilated, angular, variably sized glands in the subcapsular region, varying proportions of nonluminal tumor cells, and a background of central fibrosed hyalinized stroma. The appearance is that of a low-grade carcinoma. Focal higher grade carcinoma was superimposed on this histologic data in three cases. Neither recurrences nor metastases were seen in 11 of 12 patients after surgical resection with a follow-up of 1.2 to 13 yrs (mean, 4.2 years). Ploidy studies were performed on the paraffin-embedded tissue in 11 cases and yielded results for 7 cases. Aneuploid cell populations were found in five tumors; two had normal diploid populations; and the ploidy results are not predictive of tumor behavior. This type of salivary gland tumor fits diagnostically within the category of noninvasive and minimally invasive carcinoma ex pleomorphic adenoma (also referred to as in situ and low-grade malignant mixed tumors), a class that requires additional awareness and precise recognition as it signifies a good prognosis after surgical resection.

Adenoma, Pleomorphic

Myoepithelial cells actively proliferate during atrophy of rat parotid gland.

Despite limited supporting evidence, salivary gland myoepithelial cells are said to be differentiated cells with little or no capacity to replicate; they presumably develop from stem cells. This study investigated the proliferative potential of myoepithelial cells with an antibody to proliferating cell nuclear antigen and a rat model. This model involved clamping of the parotid duct causing atrophy of the gland and then releasing the duct followed by gland regeneration. Rats were sacrificed at time points during atrophy and regeneration phases and the number and location of cycling myoepithelial cells assessed. Cycling myoepithelial cells were identified with double immunohistochemical staining, cycling cells with proliferating cell nuclear antigen-positive nuclei within muscle-specific actin-positive cytoplasm (the latter identified with antibody HHF35). The results show that baseline proliferative rates of myoepithelial cells in both the resting and fully regenerated gland ranged from 0.3% to 2%, similar to rates for other major cell types in the normal rat gland. A peak myoepithelial cell proliferative rate of 23% occurred at day 5 during the atrophy phase. Rates during the regenerative phase were not significantly different than the baseline levels. Similarities of rat and human parotid gland and the definite proliferative capacity of myoepithelial cells indicates that these specialized cells must be considered one of the potential progenitor cells for human salivary gland tumors.

Actins

Differentiating myoepithelial and acinar cells in rat neonatal parotid gland and histogenetic concepts for salivary gland tumors.

Histogenetic concepts for salivary gland tumors are predicated on the presence of reserve or undifferentiated cells in normal glands, presumably the source for cell renewal and induction of tumors. Developing rat parotid gland, which remains fetal-like at birth, provides the opportunity to study differentiation and observe whether cytologically undifferentiated cells do or do not have functional indicators of specific differentiation pathways. Immunohistochemistry and immuno-electron microscopy, when applied to parotid gland at birth, at 12 days of age and in the adult gland, indicate that commitment to myoepithelial cell differentiation occurs prior to development of structural changes characteristic of these cells. Conversely, secretory granules are evident in differentiating acinar cells prior to synthesis of amylase. The results suggest that an appearance of undifferentiation does not confer reserve cell status either in the normal salivary gland or their tumors.

Actins

Diagnostic criteria for neoplastic myoepithelial cells in pleomorphic adenomas and myoepitheliomas. Immunocytochemical detection of muscle-specific actin, cytokeratin 14, vimentin, and glial fibrillary acidic protein.

OBJECTIVE: Markers for normal salivary gland myoepithelium were used to determine the extent of their expression in the neoplastic myoepithelial (nonluminal) cells of pleomorphic adenomas and then in the tumor cells in myoepitheliomas and to gather information necessary to establish diagnostic criteria, especially muscle actin expression, for myoepitheliomas. STUDY DESIGN: Methanol/acetic acid-fixed and paraffin-embedded tissue was used to immunohistochemically study expression of intermediate and smooth-muscle actin filaments in nonluminal cells in 14 pleomorphic adenomas and to compare this to their expression in five myoepitheliomas. RESULTS: In routine histologic sections, the morphologic variants of nonluminal tumor cells--spindle, stellate, polygonal, angular, and plasmacytoid--in pleomorphic adenoma mirror the spectrum of tumor cells in myoepitheliomas. Immunocytochemical similarities are also apparent. Two specific markers for myoepithelial cells in the normal salivary gland, muscle-specific actin and cytokeratin 14, were both variably, independently, and never uniformly expressed in nonluminal cells of pleomorphic adenoma and tumor cells in myoepitheliomas regardless of their morphology. Cytokeratin 14 in addition labels basal cells of excretory ducts. Both muscle-specific actin and cytokeratin 14 preferentially localized to single layers of periductal cells in pleomorphic adenomas, angular, polygonal, and plasmacytoid cells preferentially expressed cytokeratin 14. Similar patterns were noted in the three myoepitheliomas with reasonable expression of the two markers. Only isolated single cells or small groups of plasmacytoid cells in four pleomorphic adenomas with a significant component of these cells and the two plasmacytoid myoepitheliomas immunostained for muscle-specific actin and cytokeratin 14. In both tumor types, vimentin was nearly uniformly expressed in nonluminal tumor cells of all morphologic types, including plasmacytoid cells. CONCLUSIONS: The range and transition of morphology of nonluminal cells in pleomorphic adenomas is reflected in myoepitheliomas. Incomplete or absent expression of the myoepithelial/basal cell markers, muscle-specific actin, and cytokeratin 14, and the general expression of vimentin is common to both tumors. Because these findings apply to the majority of plasmacytoid cells in pleomorphic adenomas, tumor cells with a similar morphology and immunoprofile are to be expected in myoepitheliomas; the term plasmacytoid myoepitheliomas is thus appropriate regardless of the presence or absence of muscle-specific actin.

Actins

Malignant myoepithelioma of the parotid gland: case report and review of the literature.

A 62-year-old male with a myoepithelioma of the right parotid gland was treated with surgical excision followed by adjuvant radiation therapy. Prior to the completion of radiation therapy, the patient developed progressive disease at local, regional, and distant metastatic sites. Combined modality treatment with radiation and chemotherapy resulted in a significant but transient shrinkage of the tumours at all sites. The patient succumbed to metastatic disease 212 days following the diagnostic biopsy. This case illustrates several of the distinctive clinical and pathological characteristics of this rare tumour.

Humans

Clinico-pathological predictors of recurrence for acinic cell carcinoma.

The biological behaviour of acinic cell carcinomas, even if well differentiated, is unpredictable. We studied 45 patients with acinic cell carcinoma followed-up from 10 to 379 months (5 year recurrence-free and survival rate of 69% and 81% respectively), and compared clinico-pathological parameters with outcome. The presence of a predominately solid architecture was strongly associated with a poor outcome (P < 0.01) and this was the only independent prognostic variable when log rank testing was performed. Tumour size (> 2.75 cm) was a significant predictor of recurrent deep parotid lobe involvement, the presence of cervical nodal disease and lymphocytic infiltration, although not significant, factors showed a tendency towards recurrence. For acinic cell carcinoma, the predominant solid architecture would appear to be a strong predictor of recurrence.

Adolescent

Postirradiated submandibular gland: a potential model to study salivary gland radioprotection and tumourigenesis.

Theoretical reserve cells located in the intercalated and excretory ducts are postulated to be responsible for salivary gland tumourigenesis, with acinar cells playing no role in this process. Animal models, one using low-dose radiation to rat submandibular glands, indicate that this hypothesis is incorrect. Few human models have been devised to demonstrate and verify this theory. Submandibular glands in the field of ionizing radiation, as external-beam radiotherapy for head and neck tumours, were examined using an immunocytochemical technique and an antibody to proliferating cell nuclear antigen (PCNA), a specific marker for cycling cells. In the nonirradiated gland, nuclei positive for PCNA were seen in acinar as well as ductal cells of all types. Six months post irradiation, human submandibular glands show increased proliferative rates in both ductal and acinar cells that are significantly greater than control glands (p = .012). Based on this regenerative capacity, postirradiated human submandibular glands might serve as a model to investigate various treatment modalities for the prevention of radiation damage to acinar cells and the consequent patient morbidity that develops due to xerostomia. As well, these results suggest that even in humans, acinar cells are potential targets for carcinogenic agents and that current histogenic concepts for salivary gland tumourigenesis are incorrect.

Adult

Pathology of the salivary glands: the contribution of electron microscopy.

Electron microscopy has a limited role in the diagnosis of primary salivary gland tumors, although it can be helpful in metastatic lesions of possible salivary gland origin. The diversity of subtypes in salivary gland tumors, as well as the range of histomorphology within any one subtype, is unparalleled in any other human tumor. This and their relative infrequency causes diagnostic problems for pathologists. Ultrastructural techniques have been of major importance in determining the inter-relationship of these tumors for classification purposes, revealing the subtle variations in common cellular differentiation pathways, determining the organization of tumor cells, and displaying the importance of extracellular matrix materials in establishing diagnostic criteria for each of the many subtypes. Electron microscopy has also been valuable in non-neoplastic salivary gland disease and has an increasing role in experimental studies involving tissue from human and animal salivary parenchyma.

Animals

Acinic cell carcinoma of salivary glands. Prognostic relevance of DNA flow cytometry and nucleolar organizer regions.

OBJECTIVE: To test the prognostic ability of flow cytometry and counts of silver-enhanced intranuclear nucleolar organizing regions (AgNORs) in acinic cell carcinoma. DESIGN: Using statistical methods to establish if analysis of DNA content, percentage DNA synthetic (S)-phase, and the AgNOR counts on 45 cases of acinic cell carcinoma with clinical follow-up ranging from 10 to 379 months are predictors of time to recurrence or time to death due to acinic cell carcinomas. MAIN OUTCOME MEASURES: Whether tumors with low AgNOR counts and diploid DNA are favorable acinic cell carcinomas and the converse, aneuploid DNA and elevated AgNOR count, predict unfavorable neoplasms. RESULTS: Tumors with a diploid DNA content had as unfavorable a clinical course as aneuploid acinic cell carcinomas. Similarly, S-phase and AgNOR count results showed considerable overlap when separated into carcinomas with or without local recurrence, metastasis, or death due to tumor. Statistical evaluation also failed to provide predictors of clinical course based on ploidy, percentage S-phase, or AgNOR counts. CONCLUSION: The results, although negative, are important in showing that data on DNA content, cell cycle, and nuclear limits useful in other neoplasms are of limited practical application in establishing predictors of time to recurrence or time to death in acinic cell carcinomas. Solving the enigmas, for clinicians and pathologists, associated with acinic cell carcinomas will require further information about the biology of this neoplasm.

Adult

Relationship of clear cell oncocytoma to mitochondrial-rich (typical) oncocytomas of parotid salivary gland. An ultrastructural study.

Nosologically, the designation clear cell oncocytoma seems illogical and contradictory when the definition of an oncocytoma relies on mitochondrial-rich cells; its relationship to the granular (mitochondrial-rich) oncocytoma needs further clarification. Electron microscopy of six examples of oncocytoma from five patients allowed assessment of cellular features in three clear cell variants, two typical oncocytomas and one with a roughly equal proportion of clear and granular tumor cells. Ultrastructurally, in the clear cell types of oncocytoma, a considerable to extensive portion of the central cytoplasm was occupied by monoparticulate glycogen with margination of mitochondria and other organelles. The degree of extraction of the glycogen during fixation and processing accounts for variation in the extent of the clear cell component as phosphotungstic acid-hematoxylin staining reveals considerable mitochondria in many of the tumor cells in the clear cell variant of oncocytoma. Ultrastructural findings further support an interrelationship between clear and granular cells, as some typical oncocytes are evident in the clear cell variant of oncocytoma, and one oncocytoma in this series had a roughly equal number of glycogen-rich and mitochondrial-rich tumor cells both of which took part in the formation of microlumens. The designation clear cell oncocytoma is appropriate within the oncocytoma subgroup of salivary gland tumors.

Adenoma, Oxyphilic

Analysis of c-erbB-2 amplification in salivary gland tumours by differential polymerase chain reaction.

DNA samples extracted from 22 normal salivary glands, 38 salivary pleomorphic adenomas and 20 other salivary gland neoplasms were screened for amplification of the c-erbB-2 oncogene by a differential polymerase chain reaction (PCR). The samples were PCR amplified with primers specific for the c-erbB-2 oncogene and for a reference gene (interferon-gamma). A breast carcinoma cell line SKBR-3 known to contain c-erbB-2 amplification was used as positive control. Following gel electrophoresis, the intensity of the amplified DNA bands was determined by laser densitometry and the level of amplification of the c-erbB-2 oncogene was assessed from the intensity of the c-erbB-2 specific band relative to that of the interferon-gamma band. Of all the tumours detected, only the two poorly differentiated adenocarcinomas, two of the pleomorphic adenomas and one of the Warthin's tumours showed gene amplification at levels comparable to the breast carcinoma cell line. None of the normal salivary gland tissues was found to have amplification. Within the group of pleomorphic adenomas the average level of amplification was not significantly different from that observed in the normal salivary gland, or in total genomic DNA from unrelated tissue (P < or = 0.001, determined by a general linear model of statistical analysis). These results indicate that amplification of the c-erbB-2 oncogene is infrequent in salivary neoplasia. Thus, gene amplification alone cannot account for the high prevalence of c-erbB-2 overexpression demonstrated previously in salivary gland tumours. When present, c-erbB-2 amplification may be associated with a more aggressive behaviour.

Adenoma

The pathobiology of salivary gland. III. PCNA-localization of cycling cells induced in rat submandibular gland by low-dose x-radiation.

Application of ionizing radiation to adult rat major salivary glands tested tenets of the bicellular reserve cell hypothesis for the induction of salivary gland tumors, namely, that stem cells preferentially located to luminal cells of the intercalated duct and basal cells of the excretory duct in normal salivary glands. The effect of a single, low dose (3000 cGy) of x-radiation administered to the parotid and submandibular glands was followed with the use of immunocytochemistry and an antibody to the cell cycle-related protein proliferating cell nuclear antigen to detect the kinetics and localization of cycling cells up to 15 days postirradiation. Maximal responses occurred in acinar cells (12.6-fold increase) of submandibular glands on day 7 postirradiation. Similar but less dramatic concurrent increases in proliferating cells were evident in intercalated (3.4-fold) and striated (2.2-fold) duct cells, but little response was seen in basal or luminal cells of submandibular gland excretory ducts. A limited but maximal proliferative response again occurred on day 7 in the parotid gland. Neither in the steady state nor irradiated submandibular gland was there evidence of specific stem ("reserve") cells associated with the intercalated or excretory ducts. It appears unnecessary to invoke stem cells in a model of cellular proliferation in salivary glands. Therefore current concepts of salivary gland tumorigenesis require modification because all cell types, including acinar cells, are at risk in the carcinogenic process.

Animals

Demonstration of c-erbB-2 oncogene overexpression in salivary gland neoplasms by in situ hybridization.

The level of c-erbB-2 cellular mRNA in 18 salivary gland tumours and in 7 normal salivary glands was determined by in situ hybridization using [35S] labelled RNA probes. Computer assisted quantitation of the autoradiographic signal indicated a significantly higher c-erbB-2 expression in the tumour group (22.64 grains per cell +/- 3.79; 95% CI) as compared to the non-neoplastic salivary gland tissue (4.11 +/- 0.90; 95% CI). The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29 +/- 1.87; 95% CI), mucoepidermoid carcinomas (31.52 +/- 0.08; 95% CI) and the acinic cell carcinomas (44.24 +/- 17.11; 95% CI) were significantly greater than the expression for the normal group. The acinic cell carcinomas exhibited the greatest level of expression. As observed at the individual cell level, the autoradiographic signal was distributed uniformly in the neoplastic tissues, regardless of the cell type. This study confirms the hypothesis that the c-erbB-2 oncogene is overexpressed at the mRNA level in salivary gland tumours.

Adenoma, Pleomorphic

Collagen gel cultures of normal salivary gland: conditions for continued proliferation and maintenance of major cell phenotypes in vitro.

The presence of three functionally and phenotypically distinct epithelial cell populations--acinar, duct, and myoepithelial cells--in major salivary glands creates problems when developing physiologically appropriate culture systems for the study of these tissues in vitro. Previous attempts to establish cultures of rat submandibular gland resulted in continued proliferation and maintenance of glandular architecture, but loss of distinct features of differentiation of the three epithelial cell types. The present study describes an ultrathin free-floating collagen gel culture technique (mantle gels). Using this method, immunohistochemical and ultrastructural studies indicate that rat submandibular gland continues to cycle, and secretory activity and phenotypic markers for acinar, duct, and myoepithelial cells are all demonstrable after 4 weeks in culture, suggesting that this constitutes the ideal system for in vitro investigation of the pathobiology of the salivary gland.

Animals

Detection of proliferating cell nuclear antigen in paraffin-embedded specimens is dependent on preembedding tissue handling and fixation.

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), a cell cycle-related protein used to estimate tumor growth fraction, is variable in formalin-fixed compared with methanol-fixed tissue specimens. This is assumed to result from conformational changes in the antigenic epitope induced by formaldehyde; therefore, to be susceptible to retrieval in archival specimens. In this study, formalin fixation reduced the intensity of staining and the number of positive cells to approximately 25% of those in methanol-fixed material. The washing of tissue specimens prior to methacarn fixation also reduced PCNA staining. Loss of staining was not restored after use of a commercial retrieval kit recommended for PCNA immunohistochemistry. Immunoblotting of formalin fixatives and saline washings after removal of tissue specimens consistently demonstrated the presence of PCNA-like activity in solution. We conclude that the exceptional solubility of PCNA is responsible for reduced immunostaining in formalin-fixed material, that the loss is irreversible, and that methanol or methacarn is the fixative of choice for PCNA immunohistochemistry.

Animals

Kimura's disease: an unusual cause of head and neck masses.

This article presents a case report of a patient who presented with Kimura's disease. Kimura's disease is an unusual condition with predilection to involve the head and neck. Since Kimura's disease often imitates a neoplastic or inflammatory process of the head and neck it behooves the otolaryngologist-head and neck surgeon to be able to recognize this entity.

Adult