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At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Resistance of muscle to tumor metastases: a role for a3 adenosine receptor agonists.

Tumor metastases are extremely rare in striated muscles. Lately, we have found that muscle cell conditioned medium (MCM) inhibits the proliferation of various tumor cells while maintaining the growth of normal murine bone marrow cells. This dual activity was confirmed in vivo when the MCM was administered orally, i.e., it inhibited the development of tumor growth in mice and prevented the myelotoxic effects of chemotherapy. Adenosine was found to be one of the active components of MCM, inhibiting tumor cell growth while maintaining bone marrow cell proliferation in vitro. Adenosine is known to act as an important regulatory molecule through its binding to specific G-protein-associated A1, A(2a), A(2b) and A3 cell surface receptors. In distinction from MCM, adenosine did not suppress tumor development in mice and was not active as a chemoprotective agent when administered orally or intravenously. Thus, the in vivo activity of MCM could not be attributed to adenosine. In this study, MCM from which adenosine was enzymatically removed still retained its dual activity that was also found to be mediated through the A3 adenosine receptor (A3AR). This result led to the conclusion that natural agonists to A3AR were responsible for the activity of MCM. We further tested synthetic agonist to the A3AR and demonstrated that it possessed the same in vitro and in vivo activity profile as MCM. Taken together, muscle cells, in addition to adenosine, secrete natural agonists to A3AR. These agonists are stable nondegradable molecules and may contribute to the systemic anticancer and chemoprotective activity exerted by MCM. This group of molecules may account for the rarity of tumor metastases in muscle.

Adenosine↗
PubMedDate not supplied

Planned preoperative radiation therapy in muscle invasive bladder cancer; results of a meta-analysis.

BACKGROUND: The role of pre-operative radiation therapy in the treatment of muscle invasive bladder cancer is unclear. The objective of this report is to present a meta-analysis of the published clinical trial data on this topic to determine whether pre-operative radiation improves survival in patients with this disease. METHODS: Data from 5 randomized trial were pooled using the meta-analytic techniques previously described by Peto et al. Three and five year survival were compared between patients receiving pre-operative radiation therapy followed by cystectomy versus patients treated with cystectomy alone. RESULTS: A summary odds ratio was calculated following a statistical analysis showing a lack of heterogeneity among the included studies in terms of their estimate of effect. The calculated Peto odds ratio was 0.71 favoring the use of preoperative radiation (95% CI 0.48-1.06). Due to possible biases in this original analysis due to study design deficiencies, a sensitivity analysis showed a "corrected" odds ratio of 0.94 with a 95% confidence interval of 0.57- 1.55, a non-statistically significant result. CONCLUSION: The available clinical trial data do not support a role for routine use of pre-operative radiation therapy in the treatment of muscle invasive bladder cancer. Additional well designed trials are needed to address this issue.

Cystectomy↗
PubMed1989

Culture of human neoplastic gastrointestinal smooth muscle cells.

Due to limited growth potential of primary cultures and the absence of continuous lines of healthy enteric smooth muscle, we have studied the culture behavior of neoplastic gastrointestinal smooth muscle cells. Forty-six human enteric smooth muscle neoplasms (leiomyomas and leiomyosarcomas) were studied while fresh and/or after culture in vitro and growth in vivo in athymic nude mice, with assessments made of morphology, growth characteristics, and biochemical markers of differentiation. The state of differentiation of the tumors varied, with well-differentiated tumors tending to express binding sites for the gastrointestinal hormone cholecystokinin, whereas less well-differentiated tumors did not. Poorly differentiated tumors were the easiest to establish in culture in vitro and to grow in vivo in nude mice. When the cells placed directly into culture proliferated to confluent density, they underwent morphologic differentiation from a spread, fibroblastlike shape to a slender spindle morphology, with these cells possessing fewer biosynthetic organelles and arranging themselves in characteristic "hill and valley" arrays. However, the highly differentiated characteristics of expression of desmin or cholecystokinin-binding sites were not observed in cultured cells. In contrast, cells that had been passaged in nude mice before culture displayed a proliferative phenotype and failed to undergo morphologic differentiation on reaching confluent density. Four human enteric smooth muscle cell lines (documented by chromosomal analysis) originating in stomach, jejunum, ileum, and rectum were established using this strategy.

Cholecystokinin↗
PubMed2002

Expression of desmin and smooth muscle myosin heavy chain in dermatofibromas.

BACKGROUND: The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. OBJECTIVE: To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation. METHODS: We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin-stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. RESULTS: We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin-stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. CONCLUSIONS: About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.

Actins↗
PubMed2002

Epstein-Barr virus-associated smooth muscle tumour: a distinctive mesenchymal tumour of immunocompromised individuals.

immunosuppressed patients are predisposed to the development of smooth muscle tumours which show near consistent association with Epstein-Barr virus (EBV). This report describes a 37-year-old patient with acquired immunodeficiency syndrome who initially presented with two masses in the liver. Image-guided core biopsy revealed a spindle cell tumour with histological and immunological features of smooth muscle neoplasm which was shown by in situ hybridisation for EBV early RNAs to be EBV-associated. The literature on this uncommon entity is critically reviewed and the differential diagnosis is also discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1982

The effects of ageing, cachexia and neoplasms on striated muscle. Quantitative histological and histochemical observations on an autopsy material.

The effects of ageing, cachexia and neoplasms on striated muscle were examined in histological sections of an autopsy material. Paraffin sections were examined from four separate muscles of 30 previously healthy subjects who died suddenly, from eight cases with cachexia and from 16 cases with cachexia and neoplasms. In addition, ATP-ase stained cryostat sections were examined from two muscles from most of the cases. All the sections were evaluated with regard to atrophy, myopathic changes and fibre type grouping. Furthermore, the exact size of 100 fibres of each type was determined in the enzyme stained sections. Myopathic changes were found in a few muscles, mainly in the normal cases. They were considered incidental findings without clinical significance. Fibre type grouping could not be evaluated in the anterior tibial muscle because large clusters of the same fibre type occur normally in this muscle. In the biceps brachii only two normal cases and none of the cachectic cases showed fibre type grouping. A moderate small grouped muscle fibre atrophy was found in normal cases with increasing age. The cases with cachexia showed a marked small grouped atrophy which involved both fibre types. There were only small and uncertain differences between cases with cachexia and tumours and those with cachexia alone. Thus, no changes were observed which could be ascribed to tumours alone. The small grouped atrophy in ageing and cachexia resembled that seen in denervation atrophy but the exact mechanism of the changes remains obscure.

Adenosine Triphosphatases↗
PubMed1975

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx: a clinicopathologic study. IV. Smooth muscle tumors (leiomyoma, leiomyosarcoma)

In a review of nonepithelial tumors involving the nasal cavity, paranasal sinuses, and nasopharynx, 256 lesions, 156 benign and 100 malignant, were identified. Of these, 8 were smooth muscle neoplasms, 2 leiomyomas, and 6 leiomyosarcomas. The clinical findings associated with these smooth muscle tumors are described, their histologic features illustrated, results of therapy presented, and clinicopathologic correlations made. The leiomyomas were small lesions found incidentally within polypectomy specimens, and were successfully treated by polypectomy. Leiomyosarcomas could not be eradicated easily by surgery, recurred frequently, did not respond well to radiotherapy, and carried a poor prognosis.

Adolescent↗
PubMed1994

Smooth muscle and bone neoplasms in transgenic mice expressing SV40 T antigen.

Transgenic mice carrying the SV40 early region fused to the Drosophila hsp70 promoter developed smooth muscle and bone neoplasms. The smooth muscle tumors appeared in aged mice and were preferentially located on the muzzle or eyelids. Multiple neoplasms were often present and each appeared to be an independent proliferation. In contrast, the bone tumors typically developed in the petrous ridge and had all the features of osteogenic sarcomas, displaying distant metastasis and invasion of the brain. Cells in both types of tumors exhibited nuclear expression of SV40 T antigen. Mice homozygous for the transgene had a shorter latency for appearance of smooth muscle tumors and developed osteosarcomas more frequently than hemizygous mice. This model system implicates the cellular T antigen-binding proteins, such as Rb and p53, in the pathogenesis of bone and soft tissue neoplasms in mice.

Animals↗
PubMed1977

Multiple leiomyosarcomas.

A 32-year-old woman underwent a conservative total excision of a leiomyosarcoma of the sigmoid mesocolon. During the subsequent six years she developed additional malignant and benign smooth muscle neoplasms in the soft tissues and uterus which were treated only by nonmutilating surgical excisions with an excellent result. Since we know of no proof to the contrary, we submit this case as an example for surgically excising adult soft tissue sarcomas in as conservative a manner as is sufficient to locally eradicate the disease. Adjunctive radiation or chemotherapy or both may prove to be beneficial.

Adult↗
PubMed2001

Differential binding of an SRF/NK-2/MEF2 transcription factor complex in normal versus neoplastic smooth muscle tissues.

The malignant potential of smooth muscle tumors correlates strongly with the disappearance of gamma-smooth muscle isoactin, a lineage-specific marker of smooth muscle development. In this paper, we identify a 36-base pair regulatory motif containing an AT-rich domain, CArG box, and a non-canonical NK-2 homeodomain-binding site that has the capacity to regulate smooth muscle-specific gene expression in cultured intestinal smooth muscle cells. Serum-response factor associates with an NK-2 transcription factor via protein-protein interactions and binds to the core CArG box element. Our studies suggest that the NK-2 transcription factor that associates with serum-response factor during smooth muscle differentiation is Nkx2-3. Myocyte-specific enhancer factor 2 binding to this regulatory complex was also observed but limited to uterine smooth muscle tissues. Smooth muscle neoplasms displayed altered transcription factor binding when compared with normal myometrium. Differential nuclear accessibility of serum-response factor protein during smooth muscle differentiation and neoplastic transformation was also observed. Thus, we have identified a unique regulatory complex whose differential binding properties and nuclear accessibility are associated with modulating gamma-smooth muscle isoactin-specific gene expression in both normal and neoplastic tissues.

3T3 Cells↗
PubMed2006

An appendiceal leiomyoma in a child with acquired immunodeficiency syndrome.

Children with acquired immunodeficiency syndrome (AIDS) are at an increased risk for lymphoproliferative and neoplastic disorders. Included among these are smooth muscle neoplasms such as leiomyomas and leiomyosarcomas. There have been at least 15 reported cases of smooth muscle tumors in the approximately 8,000 children with AIDS, however the incidence in immunocompetent children is only two per ten million. The lesions in children with human immunodeficiency virus infection are usually found in the lung, liver, and gastrointestinal tract. Here, we present an unusual case of a 12-year-old African American girl with vertically acquired AIDS who presented to the pediatric emergency department with severe diffuse abdominal pain. She was ultimately found to have an appendiceal leiomyoma on abdominal exploration, the first reported case. Our report suggests that smooth muscle tumors of the appendix be included in the differential diagnosis of abdominal masses in children with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

MRI evaluation of thermal ablation of tumors with focused ultrasound.

MRI was used to target and evaluate the tissue effects of focused ultrasound ablation on tumors implanted in the skeletal muscle of rabbits in vivo. First, MRI was used to localize the tumors and plan the ultrasound therapy. Second, temperature-sensitive phase-difference images were acquired to monitor the location of the ultrasound focus and to estimate the effects of temperature rise. After the treatment, the spatial and temporal temperature profiles for defining boundaries of tissue coagulation were calculated. Finally, these boundaries were compared to T2-weighted and contrast-enhanced T1-weighted images obtained immediately after therapy. The results indicate that using MRI for planning and evaluating focused ultrasound surgery is feasible. We showed a linear relationship between applied power and shifts in the proton resonant frequency. Fluctuations in the location of the focus about the target location were on the order of the resolution of the MR images. The temperature rise and lesion size varied significantly. Regions of tissue coagulation calculated from MR data correlated well with post-therapy imaging.

Animals↗
PubMed2004

New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.

Animals↗