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Biomedical subjects

R P Moser

Publications and source records attributed to R P Moser.

At least 19 recordsLinked to original sources
PubMed1996

Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas.

Increasing evidence suggests the existence of polarized human T cell responses described as Th1-type (promoting cell-mediated immunity) and Th2-type (promoting humoral immunity), characterized by a dominant production of either interferon-gamma (IFN-gamma) or IL-4, respectively. Little is known about the intratumoural activation of infiltrating lymphocytes (TIL) in human gliomas. Therefore, we assessed fresh TIL at cellular and molecular levels to find out if they were activated and polarized into a type 1 or 2 immune response. Flow cytometry analysis of TIL revealed that the major subset was made of T lymphocytes. Double labelling with alpha-CD3 and adhesion/ activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, some of which were almost absent in autologous T peripheral blood lymphocytes (T-PBL). Furthermore, the proportions of T-TIL expressing CD56, CD65, or CD25 were several-fold higher than in T-PBL. Intratumoural functional activation of TIL was tested by semiquantitative assessment in relative units (RU) of lymphokine gene activation with mRNA reverse transcriptase-polymerase chain reaction (RT-PCR). All TIL populations except one significantly expressed IL-4 1 to 2 logs of RU above healthy PBL baseline. Similarly, all patients expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) in a range comparable to IL-4. However, most TIL populations did not express IFN-gamma, IL-2, and tumour necrosis factor-beta (TNF-beta) at higher levels than healthy normal PBL. The increase proportion of T cells expressing activation markers and the consistent detection of significant IL-4 and GM-CSF lymphokine gene activation in TIL populations suggested a predominant type 2 intratumoural immune response that does not promote cell-mediated tumouricidal activity and may contribute to the inefficiency of the antiglioma immune response.

Genes, Immunoglobulin↗
PubMed1996

Anterior transcranial (craniofacial) resection of tumors of the paranasal sinuses: surgical technique and results.

Transfacial approaches, traditionally used for malignant tumors of the paranasal sinuses, provide limited exposure when several sinuses are involved and are unsuitable for tumors that erode through the floor of the anterior cranial fossa. A transcranial approach may aid in the removal of such lesions. To better understand the risks and benefits of this surgical approach, we reviewed all patients (n = 76) who underwent a transcranial approach as part of the excision of paranasal sinus lesions between 1984 and 1993 at our institution. The spectrum of disease included adenocarcinoma (13 patients), squamous cell carcinoma and olfactory neuroblastoma (11 patients each), adenoid cystic carcinoma and poorly differentiated forms of carcinoma (6 patients each), melanoma (5 patients), and miscellaneous others (24 patients). Most patients had ethmoid sinus involvement; tumors were also commonly found in the cribriform plate, sphenoid sinus, and nasal fossa. In each patient, a bifrontal craniotomy was performed with extradural dissection to the floor of the anterior fossa and osteotomies for resection of involved elements. In 47 patients (62%), disease in the orbit, the anterior nasal cavity, or the soft tissues of the face required transfacial as well as transcranial resections. Bony defect in the anterior fossa floor was repaired with a pedicled pericranial flap. Patients with major complications included six patients with epipericranial and/or epidural hematomas requiring evacuation, three with transient cerebrospinal fluid leaks, two who developed bifrontal cerebral infarcts, and one who died soon after surgery. No meningitis was seen. To date, 26 patients (34%) have died; of those living (mean follow-up, 34 mo), 42 (84%) remain in full remission. The transcranial approach can achieve removal of erosive, invasive tumors from this area with predictable morbidity and may be considered whenever sinus tumors breach the anterior cranial base or extend beyond the reach of conventional transfacial approaches.

Adolescent↗
PubMed1995

Little expression of cytokine mRNA by fresh tumour-infiltrating mononuclear leukocytes from glioma and lung adenocarcinoma.

We investigated whether cytokine genes were activated in human tumour-infiltrating mononuclear leukocytes (TIML) obtained from six lung adenocarcinomas and seven glioblastomas. TIML were extracted by mechanical disruption and isolated by double density gradient of Ficoll. We performed mRNA reverse transcription-polymerase chain reaction (RT-PCR) on these fresh (noncultured) TIML and autologous peripheral blood mononuclear leukocytes (PBML) using primers for the cytokines IL-1 beta, IL-6, IL-2, IL-4, GM-CSF, IFN-gamma and TNF-beta. In addition, we compared patients' TIML and PBML populations with healthy normal and alpha-CD3 activated PBML as an optimally activated reference population. Gel bands of RT-PCR products were quantitated in relative units (RU) as a function of their size and intensity by computerized image-analysis. Lung and brain patients' TIML showed IL-1 beta and IL-6 cytokine mRNA expressed in the average of 2-log RU but not significantly different from autologous and normal healthy PBML. IL-2, IFN-gamma and TNF-beta also did not appear expressed in the TIML at higher levels than in autologous or healthy normal PBML. However in two thirds of patients, lung TIML could be distinguished from autologous PBML by specific expression of GM-CSF and from healthy normal PBML by expression of IL-4. Similarly, most brain TIML expressed mRNA significantly above healthy normal PBML for GM-CSF and IL-4. In comparison with alpha-CD3 activated healthy PBML, our results suggest that lung and brain TIML had detectable cytokine mRNA, but they seemed poorly activated in total number of genes and amount of cytokine mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Comparison of cell adhesion molecule expression between glioblastoma multiforme and autologous normal brain tissue.

We investigated glioblastoma multiforme (GBM) for a pattern of consistent alterations in cell adhesion molecules (CAM) expression that might distinguish tumor from normal autologous brain tissue. We used frozen section immunohistochemistry with anti-CAM and computerized image analysis to quantify staining intensity which we expressed as relative intensity units (RIU). Our results showed that normal brain tissue generally did not express alpha 1 beta 1, intercellular CAM-1 (ICAM-1), and sialylated Lewisx, slightly expressed alpha 2, alpha 4, alpha 5, alpha 6 beta 1, alpha v beta 3, lymphocyte function-associated antigen-3 (LFA-3), Lewisx, sialylated LewisLewisx, had a good expression of alpha 3 beta 1 and CD44, and strongly expressed neural CAM (NCAM). GBM expressed alpha 2, alpha 3, alpha 5, alpha 6 beta 1, alpha v beta 3, ICAM-1, LFA-3, CD44, Lewisx, sialylated Lewisx, and sialylated LewisLewisx significantly higher (2-11-fold RIU) than normal brain tissue. ICAM-1 and LFA-3 were the most distinctive markers of GBM. The small blood vessel endothelial cells of the normal brain and the GBM showed a few differences. The tumor endothelium expression of alpha 2 beta 1, alpha 4 beta 1, and LFA-3 RIU appeared twice higher than in normal endothelium and alpha 6 beta 1 showed an average of 40% RIU decrease in comparison to normal. These results show that the expression of several CAM is consistently altered in GBM and its microvasculature when compared with autologous normal brain tissue.

Antigens, CD↗
PubMed1995

MR imaging of periarticular soft-tissue lesions.

The exquisite soft-tissue contrast and multi-planar imaging capabilities of MR imaging uniquely qualify this modality for the evaluation of periarticular pathology. MR evaluation can be diagnostic by signal characterization, as in a lipoma, or by anatomic location, as seen in meniscal and synovial cysts. In other less diagnostic pathology, MR imaging can focus a differential diagnosis, guide percutaneous or surgical biopsy, provide local staging, and serve as a surgical map.

Biopsy↗
PubMed1994

Sequential TNF and TGF-beta regulation of expansion and induction of cytotoxicity in long-term cultures of lymphokine-activated killer cells.

Therapeutic use of lymphokine-activated killer (LAK) cells frequently requires higher numbers of effector cells than can be produced in short-term cultures. Extended stimulation of these cells by interleukin-2 (IL-2) past 2 weeks leads to a decrease in cytolytic activity and cell proliferation. To determine how known regulatory cytokines are involved in the mechanism responsible for loss lf IL-2 responsiveness, adherent LAK (A-LAK), nonadherent LAK (NA-LAK), monocyte-depleted (MD-LAK), and unmanipulated LAK (UN-LAK) cells derived from human peripheral blood were stimulated with high-dose IL-2 for 4 weeks, and cytokine production was measured serially. Despite continued supplementation with IL-2, cell number plaeaued at 2 weeks with a 2.5-3.0 log increase in A-LAK cultures and a 1.0 log increase in NA-LAK, MD-LAK, and UN-LAK cultures. Cytolytic activity had decreased significantly in all four culture systems after only 14 days of stimulation with IL-2 as assessed by the chromium release assay using K562, Daudi, and RP-mel tumor cell lines as targets, and LAK activity was barely detectable after 28 days of stimulation. Bioactive tumor necrosis factor (TNF) was present in concentrations of 15-55 U/ml during the first week of culture and at less than 10 U/ml thereafter. Bioactive transforming growth factor-beta (TGF-beta) was detected at 1-36 U/ml from 5 to 14 days of culture and decreased thereafter. Immunoreactive TGF-beta 2 was still present at concentrations of 20-90 pg/ml after 21 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of anti-CD3/anti-CD28/interleukin-2 stimulation of mononuclear cells on transforming growth factor beta inhibition of lymphokine-activated killer cell generation.

After simultaneous stimulation with anti-CD3 monoclonal antibody (mAb) at 10 ng/ml, anti-CD28 mAb at 125 ng/ml, and interleukin-2 (IL-2) at 20 U/ml, peripheral blood mononuclear cells (PBMC) were partially resistant to immunosuppression by transforming growth factor-beta (TGF beta 2). The doses of TGF beta 2 that inhibit cytotoxicity of IL-2 stimulated cells by 60%-70% were much less effective when the same cells were stimulated with anti-CD3/anti-CD28/IL-2. This favorable stimulation a generated a cell population characterized by high lytic activity, excellent expansion, and a greater resistance to immunosuppressive action of TGF beta 2. The secretion of secondary cytokines important for LAK generation is considered a crucial event, at least partially responsible for the antagonization of TGF beta immunosuppression.

Antibodies, Monoclonal↗
PubMed1993

Detection of p53 alterations in human astrocytomas using frozen tissue sections for the polymerase chain reaction.

The polymorphism of amino acid residue 72 on the human p53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of the p53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in the p53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of the p53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of the p53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of the p53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas. astrocytomas.

Astrocytoma↗
PubMed1993

Cartilaginous bone tumors.

Cartilaginous tumors can be subdivided into several categories according to the following three criteria: (1) Is the lesion benign or malignant? (2) Is the lesion a pure or impure cartilaginous tumor? (3) Is the epicenter of the lesion intraosseous, juxtacortical, or in the soft tissues? This article focuses on the four most common benign cartilaginous tumors, enchondroma, osteochondroma, chondroblastoma, and chondromyxoid fibroma, and on chondrosarcoma. It reviews the biologic and developmental considerations of each and discusses in depth the basic concepts in the radiologic diagnosis of cartilaginous tumors.

Bone Neoplasms↗
PubMed1993

Ewing's sarcoma.

Ewing's sarcoma is a highly malignant tumor of uncertain origin. A strong relationship is suggested between Ewing's sarcoma and tumors of neural origin. The radiologic manifestation of Ewing's sarcoma are protean and lesions may be lytic, mixed lytic-sclerotic, or rarely, predominantly sclerotic. The lower extremity long bones are predominantly affected and most lesions are diaphyseal or metadiaphyseal. CT and particularly MR imaging are invaluable in further delineating the extent of disease not readily manifested on plain radiographs. Gallium scintigraphy and gadolinium-enhanced MR images are best for following the response to therapy. Ewing's sarcoma must be distinguished from other round cell tumors including lymphoma, neuroblastoma, and primitive neuroectodermal tumor of bone as well as from osteosarcoma.

Bone Neoplasms↗
PubMed1993

Imaging of soft tissue tumors.

In summary, MR imaging is the preferred modality for the evaluation of a soft tissue mass after plain films have been taken. The radiologic appearance of certain soft tissue tumors or tumorlike processes such as myositis ossificans, benign fatty tumors, intramuscular hemangiomas, pigmented villonodular synovitis, and certain hematomas may be sufficiently unique to allow a strong presumptive radiologic diagnosis. It must be emphasized that MR cannot reliably distinguish between benign and malignant lesions, and when radiologic evaluation is nonspecific, one is ill advised to suggest a lesion is benign or malignant solely on the basis of its MR appearance. CT may be useful in specific instances for the identification of subtle soft tissue mineralization in those patients in whom lesions are not adequately evaluated by radiographs. Ultrasonography may be useful in the assessing of recurrent disease as well as in establishing tumor vascularity.

Diagnosis, Differential↗
PubMed1992

Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein).

Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme-linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone.

Adenocarcinoma↗
PubMed1992

Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma.

Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-infiltrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) V alpha or V beta regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bllod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2-5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in V beta 8+ cells (10/42, P less than 0.05), V beta 6.7+ cells (7/42, P less than 0.05), and V alpha 2+ cells (7/42, not significant). Oligoclonal expansion of V beta 8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P less than 0.05), whereas that of V beta 6.7+ cells and V alpha 2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-gamma, but not IL-2 or IL-4. Subcutaneous tumor-specific (V beta 8+ cells) and non-specific (V beta 6.7+ cells and V alpha 2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.

Antibodies, Monoclonal↗
PubMed1992

Case report 716. Soft-tissue metastasis in synovial sarcoma.

We describe the case of a 21-year-old woman with a synovial sarcoma of the thigh, who exhibited a soft-tissue metastasis to the shoulder approximately 3 months after her initial presentation. Due to its increasing availability and the recognized importance of MRI in the preoperative evaluation of patients with soft-tissue masses, it is important to be aware of even the uncommon manifestations of frequently encountered soft-tissue sarcomas.

Adult↗