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Richard T Cheney

Publications and source records attributed to Richard T Cheney.

18 recordsLinked to original sources

Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.

BACKGROUND: Friend leukaemia integration-1 (FLI-1) antibody is a useful marker for Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and vascular tumours. However, it is also expressed in subsets of lymphoblastic lymphoma, Merkel cell carcinoma (MCC) and desmoplastic small round cell tumour (DSRCT). AIM: To determine expression of FLI-1 in various benign and malignant neoplasms, by immunohistochemical analysis on 4323 tumours using multiple tumour microarrays, as well as on whole sections. RESULTS: FLI-1 was expressed in 46/62 EWS/PNETs, 2/3 olfactory neuroblastomas, 7/102 small cell carcinomas of the lung, 10/34 MCCs, 1/14 rhabdomyosarcoma, 19/132 non-Hodgkin's lymphomas, 2/3 DSRCTs, and in 53/74 benign and malignant vascular tumours. In addition, 27/508 squamous cell carcinomas, 19/837 adenocarcinomas, 10/400 urothelial bladder cancers, 1/40 basal cell carcinomas, 3/29 liposarcomas, 1/40 glioblastoma multiforme and 9/29 medullar carcinomas of the breast expressed FLI-1. The sensitivity and specificity of FLI-1 to distinguish EWS/PNET from all types of malignancies were 74.2% and 96.0%, respectively. Finally, the sensitivity and specificity of FLI-1 to distinguish EWS/PNET from other small round cell tumours (SRCTs) were 74.2% and 91.6%, respectively. CONCLUSION: This study was the first to show that FLI-1 can be seen in a variety of solid tumours, some of which had never been explored before. This finding should be kept in mind, especially when using FLI-1 as a marker for finding the primary origin of poorly differentiated metastatic tumour. Finally, despite the expression of FLI-1 in numerous malignancies, it is still considered to be highly sensitive and specific in distinguishing EWS/PNET from other tumour types in general and from other SRCTs in particular.

Biomarkers, Tumor↗

Genetic alterations in urothelial bladder carcinoma: an updated review.

New oncogenes and tumor suppressor genes that play an important role in the pathogenesis of urothelial bladder carcinoma have been discovered. The objectives of this review were to summarize the most important oncogenes and tumor suppressor genes involved in urothelial carcinoma and to address their role in pathogenesis, their prognostic value, and their potential use as therapeutic targets. The collected data led the authors to propose a common pathway in which the fibroblastic growth factor receptor 3 (FGFR3) mutation seems to be the earliest genetic abnormality responsible for the transformation from normal tissue to atypia and dysplasia. Three different progression pathways were proposed: The first operative pathway is from dysplasia to superficial papillary pathologic Ta (pTa) tumors to pT1 tumors and, ultimately, to pT2 tumors with FGFR3 and tuberous sclerosis complex 1 (TSC1) the responsible genes. The second major operative pathway is from dysplasia, to carcinoma in situ, and to solid pT1 and pT2 tumors. The third pathway of progression is from dysplasia to papillary T1 and pT2 tumors. The genes involved in the last 2 pathways are the p53, serine threonine protein kinase 15 (STK15), triple-function domain (TRIO), fragile histidine triad (FHIT), p63 genes; and alterations of 20q and 5p, alterations of adhesions, angiogenesis, and matrix-remodeling gene products also are involved. Finally, murine leukemia viral oncogene homologue 1 (RAF1) and CD9 are involved in the progression from papillary pT1 tumors to pT2 tumors.

Genes, Tumor Suppressor↗

Intraparotid sentinel lymph node biopsy for head and neck melanoma.

OBJECTIVE: The objective of this retrospective clinical review was to assess the safety and accuracy of intraparotid sentinel node biopsy in patients with melanoma. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients with cutaneous melanoma of the head and neck undergoing sentinel lymph node (SLN) biopsy in which the radionuclide localized to the parotid gland on preoperative lymphoscintigraphy were studied. METHODS: All patients underwent wide local excision of the tumor and intraparotid sentinel node biopsy using intraoperative gamma probe localization. RESULTS: There were 25 men and 3 women ranging in age from 34 to 81 years. The primary site was on the auricle in 14 patients: temple, 4; forehead, 5; cheek, 3; and on the neck in 2 patients, respectively. The mean Breslow thickness was 2.3 mm (range, 0.9-7.0 mm). In 27 of 28 patients, an intraparotid SLN was identified. In one patient, final pathology did not reveal lymphoid tissue despite a high count in the parotid tissue excised. Median number of SLN per patient was two. Six patients had microscopic metastases in the SLN. In two of these patients, additional microscopic lymph node metastases were found in the neck after subsequent formal lymphadenectomy. The pathologic staging for the group (n = 14) was: stage 1B, 4; 2A, 4; stage 2B, 3; and stage 3B, 3 patients, respectively. All patients are alive and without evidence of disease (mean follow up, 31 months). There were no surgical complications, specifically no patient experienced temporary or permanent facial paralysis. CONCLUSION: Intraparotid SLN biopsy for staging cutaneous head and neck melanoma is a reliable, accurate, and safe procedure.

Adult↗

Tumor vascular response to photodynamic therapy and the antivascular agent 5,6-dimethylxanthenone-4-acetic acid: implications for combination therapy.

PURPOSE: Photodynamic therapy (PDT) is a clinically approved treatment for a variety of solid malignancies. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a potent vascular targeting agent that has been shown to be effective against a variety of experimental rodent tumors and xenografts and is currently undergoing clinical evaluation. We have previously reported that the activity of PDT against transplanted mouse tumors is selectively enhanced by DMXAA. In the present study, we investigated the in vivo tumor vascular responses to the two treatments given alone and in combination. EXPERIMENTAL DESIGN: Vascular responses to (i) four different PDT regimens using the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) at two different fluences (128 and 48 J/cm(2)) and fluence rates (112 and 14 mW/cm(2)), (ii) 5-aminolevulinic acid (ALA)-sensitized PDT (135 J/cm(2) at 75 mW/cm(2)), (iii) DMXAA at a high (30 mg/kg) and low dose (25 mg/kg), and (iv) the combination of HPPH-PDT (48 J/cm(2) at 112 mW/cm(2)) and low-dose DMXAA were studied in BALB/c mice bearing Colon-26 tumors. RESULTS: PDT-induced changes in vascular permeability, determined using noninvasive magnetic resonance imaging with a macromolecular contrast agent, were regimen dependent and did not predict tumor curability. However, a pattern of increasing (4 hours after treatment) and then decreasing (24 hours after) contrast agent concentrations in tumors, seen after high-dose DMXAA or the combination of PDT and low-dose DMXAA, was associated with long-term cure rates of >70%. This pattern was attributed to an initial increase in vessel permeability followed by substantial endothelial cell damage (CD31 immunohistochemistry) and loss of blood flow (fluorescein exclusion assay). Low dose-rate PDT, regardless of the delivered dose, increased the level of magnetic resonance contrast agent in peritumoral tissue, whereas treatment with either DMXAA alone, or PDT and DMXAA in combination resulted in a more selective tumor vascular response. CONCLUSIONS: The observed temporal and spatial differences in the response of tumor vessels to PDT and DMXAA treatments could provide valuable assistance in the optimization of scheduling when combining these therapies. The combination of PDT and DMXAA provides therapeutically synergistic and selective antitumor activity. Clinical evaluation of this combination is warranted.

Aminolevulinic Acid↗

Genomic profiling of myeloid sarcoma by array comparative genomic hybridization.

Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site. In this study, seven cases of MS [stomach (1), testis (1), skin (2), and lymph node (3)] and 3 synchronous and 1 follow-up bone marrow (BM) samples were studied for genomic abnormalities using array comparative genomic hybridization (array-CGH). Array-CGH construction used approximately 5,400 bacterial artificial chromosome clones from the RPCI-11 library, spanning the human genome. Data were analyzed using the DNAcopy software and custom heuristics. All MS cases had genomic abnormalities detected by array-CGH. Unbalanced genomic abnormalities in five MS cases were confirmed by conventional cytogenetics (CC) and/or fluorescence in situ hybridization (FISH); these abnormalities included loss of 4q32.1-q35.2, 6q16.1-q21, and 12p12.2-p13.2 and gain of 8q21.2-q24.3, 8, 11q21-q25, 13q21.32-q34, 19, and 21. Array-CGH was also invaluable in identifying possible deletions, partner translocations, and breakpoints that were questionable by CC. The remaining two MS cases had genomic aberrations detected by array-CGH, but were not studied further by CC/FISH. Chromosome 8 was most commonly abnormal (3/7 cases). Identical genomic abnormalities were demonstrated in MS and in synchronous BM in two cases. These results demonstrate that array-CGH is a powerful tool to screen MS tissue for unbalanced genomic abnormalities, allowing identification of chromosome abnormalities when concurrent BM is nonanalyzable or nonleukemic.

Adult↗

Extra copies of chromosome 2 are a recurring aberration in ALK-negative lymphomas with anaplastic morphology.

The purpose of this study was to evaluate fluorescence in situ hybridization abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL) classified by World Health Organization criteria [17 primary nodal/systemic (10 ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra nonrearranged anaplastic lymphoma kinase gene loci (P=0.004) due to trisomy 2 irrespective of the following factors: B or T/null phenotype (P=0.315), diagnostic categories of systemic or cutaneous ALCL or the above-mentioned B-cell lymphomas (P=0.131), and CD30 positivity by immunohistochemistry (P=1.000). Trisomy 2 was absent in all ALK+ lymphomas (P=0.009), which showed rearranged ALK gene loci (P<0.001). Whether trisomy 2 is a primary or secondary event that leads to ALK- lymphomas cannot be determined from this study. Its presence in secondary B-cell lymphomas suggests that trisomy 2 may be a secondary cytogenetic aberration in lymphomas in general. Further investigation of this finding is necessary to further our understanding of the heterogeneous group of ALK- lymphomas.

Adult↗

Malignant glomus tumor: a case report and review of literature, focusing on its clinicopathologic features and immunohistochemical profile.

Malignant glomus tumor (MGT) is a rare, recently described neoplasm that recapitulates the appearance of the modified smooth cells of the normal glomus body. We report a case of MGT of the hand of a 48-year-old woman. Magnetic resonance imaging (MRI) showed a 2.8-cm, well circumscribed, enhancing mass on the volar aspect of the thenar region of the right hand in immediate continuity with the ulnar artery and nerve. Computed tomography scan (CT-Scan) of the chest was normal. Histologic evaluation revealed a multilobular lesion with prominent branching capillary vasculature and perivascular arrangement of sheets of tumor cells. The tumor cells were round, relatively uniform in size with distinct cell borders and perinuclear cytoplasmic clearing. They were of intermediate to high nuclear grade and showed significant mitotic activity. A wide local excision with negative margins was performed. Multiple lung metastases were evident at 8-month follow-up. To date, forty-five cases of MGT of skin and soft issue have been reported in the literature. Twelve of the forty-five cases developed metastasis. In this report, we emphasize the differential diagnosis of MGT in the skin and deep soft tissue.

Adenoma, Sweat Gland↗

Retiform hemangioendothelioma: a case report and review of the literature.

BACKGROUND: Retiform hemangioendothelioma (RH) is a rare, recently described vascular neoplasm of low malignant potential. METHODS: We report a case of RH of the foot of a 19-year-old white female. Histologically, the tumor grew as numerous elongated vessels resembling the shape of rete testis with involvement of the skin adnexal structures and subcutaneous adipose tissue. No dissection of collagen by small groups of endothelial cells was seen. Wide local excision was performed and the patient was healthy with no metastasis at 14 months follow-up. RESULTS AND CONCLUSIONS: Our case is discussed in the context of previously reported cases of RH; we also include a review of all cases of RH published to date.

Adult↗

Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors.

The rate of light delivery (fluence rate) plays a critical role in photodynamic therapy (PDT) through its control of tumor oxygenation. This study tests the hypothesis that fluence rate also influences the inflammatory responses associated with PDT. PDT regimens of two different fluences (48 and 128 J/cm(2)) were designed for the Colo 26 murine tumor that either conserved or depleted tissue oxygen during PDT using two fluence rates (14 and 112 mW/cm(2)). Tumor oxygenation, extent and regional distribution of tumor damage, and vascular damage were correlated with induction of inflammation as measured by interleukin 6, macrophage inflammatory protein 1 and 2 expression, presence of inflammatory cells, and treatment outcome. Oxygen-conserving low fluence rate PDT of 14 mW/cm(2) at a fluence of 128 J/cm(2) yielded approximately 70-80% tumor cures, whereas the same fluence at the oxygen-depleting fluence rate of 112 mW/cm(2) yielded approximately 10-15% tumor cures. Low fluence rate induced higher levels of apoptosis than high fluence rate PDT as indicated by caspase-3 activity and terminal deoxynucleotidyl transferase-mediated nick end labeling analysis. The latter revealed PDT-protected tumor regions distant from vessels in the high fluence rate conditions, confirming regional tumor hypoxia shown by 2-(2-nitroimidazol-1[H]-yl)-N-(3,3,3-trifluoropropyl) acetamide staining. High fluence at a low fluence rate led to ablation of CD31-stained endothelium, whereas the same fluence at a high fluence rate maintained vessel endothelium. The highest levels of inflammatory cytokines and chemokines and neutrophilic infiltrates were measured with 48 J/cm(2) delivered at 14 mW/cm(2) ( approximately 10-20% cures). The optimally curative PDT regimen (128 J/cm(2) at 14 mW/cm(2)) produced minimal inflammation. Depletion of neutrophils did not significantly change the high cure rates of that regimen but abolished curability in the maximally inflammatory regimen. The data show that a strong inflammatory response can contribute substantially to local tumor control when the PDT regimen is suboptimal. Local inflammation is not a critical factor for tumor control under optimal PDT treatment conditions.

Animals↗

Pleural mesothelioma with cutaneous extension to chest wall scars.

BACKGROUND: Cutaneous mesothelioma is rare but may occur following local surgical procedures for visceral mesothelioma or as a metastasis. METHODS: A patient with pleural mesothelioma, who developed papules within chest wall scars, 14 and 15 months after pleural biopsy and thoracentesis, respectively, is reported. RESULTS: Histopathology showed an epithelioid tumor forming tubulopapillary and glandular structures. The diagnosis of mesothelioma was confirmed with immunohistochemistry. Tumor cells stained characteristically for low-molecular-weight cytokeratins 5/6, calretinin, and vimentin and were negative for mucicarmine, carcinoembryonic antigen, thyroid transcription factor 1, prostate-specific antigen, gross cystic disease fluid protein, S-100, factor VIII, and CD31. CONCLUSIONS: Histologically, mesothelioma may resemble a primary adnexal neoplasm, metastatic adenocarcinoma, or angiosarcoma. Immunohistochemistry can clarify the diagnosis. Clinicians should be aware of the varied presentations of mesothelioma, as cutaneous presentations are becoming increasingly common.

Aged↗

Treatment with the tumor necrosis factor-alpha-inducing drug 5,6-dimethylxanthenone-4-acetic acid enhances the antitumor activity of the photodynamic therapy of RIF-1 mouse tumors.

DMXAA (5,6-dimethylxanthenone-4-acetic acid) is an antivascular agent that exerts its antitumor effect at least partly through the induction of tumor necrosis factor (TNF)-alpha. Photodynamic therapy (PDT), the activation of a photoreactive drug in tumor tissue with visible light, is used clinically to control solid malignancies. PDT has been shown previously to be potentiated, in mice, by the i.p. administration of recombinant human TNF-alpha. Here, we investigated the activity of DMXAA as a modifier of Photofrin-based PDT of implanted murine RIF-1 tumors. The DMXAA dose (20 mg.kg(-1)) used throughout this study had little effect on tumor growth. The combination of DMXAA and PDT led to a reduction in tumor volume and significant delays in regrowth, giving a PDT-dose modification factor of 2.81. This enhancement was found to be strongly schedule dependent. The most pronounced responses were achieved when DMXAA was administered 1-3 h before the local illumination of the tumors; less activity was observed at other intervals within +/-24 h of PDT-light delivery. Using a 2-h DMXAA-light interval, histological examination showed significantly reduced blood vessel counts (CD31 immunostaining) and marked necrosis (H&E) in the tumors given combination therapy compared with the tumors given either agent alone. Conversely, peritumoral tissue was still intact 24 h after the combined therapy. DMXAA did not augment the damage to normal mouse feet after low-dose PDT (1.5 mg.kg(-1) Photofrin); however, there was some enhancement of normal tissue phototoxicity when DMXAA was combined with high-dose PDT. The antitumor effect after DMXAA plus low-dose PDT (1.5 mg.kg(-1) Photofrin) appeared to be dependent on TNF-alpha because neutralizing antibodies to this cytokine reduced the tumor response to control levels. DMXAA by itself induced TNF-alpha in RIF-1 tumors whereas PDT did not. However, the addition of PDT after DMXAA resulted in decreases in TNF-alpha, suggesting that the enhanced antitumor activity of the combination therapy was not attributable simply to an increased induction of the cytokine by PDT over that from DMXAA alone. These observations suggest a promising new combination therapy with considerable therapeutic advantage.

Animals↗

Clinical course, risk factors, and treatment of microcystic adnexal carcinoma: a short series report.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive neoplasm of both eccrine and follicular differentiation; it commonly presents on the head and neck of white middle-aged to older patients. OBJECTIVE: To review the course, risk factors, and management of 10 patients with microcystic adnexal carcinoma (MAC) and to compare treatment outcome by either Mohs micrographic surgery or standard surgical excision. METHODS: Tumor registry databases were used to identify cases at Roswell Park Cancer Institute in Buffalo, New York. Fifteen cases that were coded as MAC were reviewed. Ten cases were subsequently confirmed to be MAC. From these cases, data were collected on patient demographics, tumor location and size, risk exposure, metastasis, treatment, and recurrence of tumors. RESULTS: The average age of the patients was 63.4, and females outnumbered males seven to three. Nine tumors were located on the head and neck area. Five patients had a history of radiation therapy, and two patients were sisters. The first-time procedure was Mohs micrographic surgery in four cases and surgical excision in six cases. Three patients in the surgical excision group needed a second procedure, two of whom thereafter underwent Mohs micrographic surgery. In the Mohs micrographic surgery group, none of the patients required a second procedure, and all of the patients were disease free at an average of 23.3 months. One recurrence was noted in the surgical excision group, and the average follow-up was 32 months. CONCLUSION: This report supports the use of Mohs micrographic surgery for tumor control with the least possible procedures. Risk factors appear to include radiation treatment, ultraviolet exposure, and possibly genetics.

Adult↗

Invasive pulmonary filamentous fungal infection in a patient receiving inhaled corticosteroid therapy.

We report a case of invasive pulmonary filamentous fungal infection in a patient with chronic obstructive pulmonary disease who was treated with a conventional dose of inhaled fluticasone in the absence of other causes of immunosuppression. This case demonstrates the potential risk for opportunistic fungal infections in patients treated with high-potency lipophilic inhaled corticosteroids.

Administration, Inhalation↗

Angiolymphoid hyperplasia with eosinophilia: a classic clinical presentation with histologic features of angiosarcoma.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease manifested by the proliferation of morphologically distinct endothelial cells. OBJECTIVE: To illustrate by a case report the clinical and varied histopathologic findings of ALHE. METHODS: A 29-year-old woman presented with a clinical picture of ALHE but had several histologic features of angiosarcoma. RESULTS: Management of this patient included repeat biopsies of the lesions, excision of the involved areas, careful histologic examination of the entire specimen, and appropriate follow-up. CONCLUSION: ALHE may present with various histologic features. Knowledge of the spectrum of benign and malignant vascular neoplasms helps manage these challenging cases.

Adult↗

Differential expression of high-affinity melatonin receptors (MT1) in normal and malignant human breast tissue.

Melatonin is a pineal hormone that strongly inhibits the growth of breast cancer cells in vitro and in vivo. We report thefirst use of immunohistochemical analysis to determine the distribution of the high-affinity melatonin receptor subtype, MTI, in human breast tissue, the hypothalamic suprachiasmatic nucleus, and skin. The MT1 antibody, which is specific for the cytoplasmic portion of the receptor, produced cytoplasmic staining in normal-appearing breast epithelial cells and ductal carcinoma cells; stromal cells, myoepithelial cells, and adipocytes were nonreactive. The majority of nonneoplastic samples (13/19 [68%]) were negative to weakly positive, while moderate to strong reactivity was seen in most cancer samples (49/65 [75%]). Thus, although MT1 receptors were detectable in normal and malignant breast epithelium, high receptor levels occurred more frequently in tumor cells (P < .001), and tumors with moderate or strong reactivity were more likely to be high nuclear grade (P < .045). These findings may have implications for the use of melatonin in breast cancer therapy.

Adult↗