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PubMedDate not supplied

Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells.

Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated neuroblastoma cell-surface structures in the killing mechanism of gammadelta T cells. Heat shock did not affect the extent of neuroblastoma killing by gammadelta cells. Recognition of neuroblastoma cells by gammadelta cytotoxic T lymphocytes is negatively regulated by major histocompatibility complex I receptors. Evidence for natural and inducible cell cytotoxicity of gammadelta T cells against human neuroblastoma cells, easy propagation, purification, and missing alloreactivity in mixed lymphocytes cultures indicates a role for this subpopulation of T lymphocytes in adoptive immunotherapy.

Adult↗
PubMed1975

Incompatibility at irrelevant H-2 specificities augments in vivo stimulation of alloaggressive cells.

Lymphoid cells of mice were sensitized in vivo either by H-2 strain-specific tumor allografts or by activation in lethally irradiated F1 hybrids and tested for cytotoxicity on 51Cr-labeled target cells. The release of 51Cr varied linearly with the logarithm to the proportion of effector lymphocytes to target cells and with the time of interaction. The release of 51Cr was immunologically specific and restricted to H-2 incompatibility. Spleen cells immune to public specificities of the target genotype were not cytotoxic. However, lymphoid cells immune to only one private specificity of a third-party target genotype were highly cytotoxic. The cytotoxicity of activated thymus cells on target cells sharing one private specificity with the genotype used for sensitization was significantly enhanced when the effector thymocytes were activated also against H-2 specificities not shared by the target strain. The results suggest that gene products that facilitate sensitization of effector cells may be determined both by the H-2K and the H-2D end of the H-2 complex. It remains to be shown whether the products of these loci, operating during sensitization in vivo, are body-wide correlated to the lymphocyte-defined specificities detectable during the mixed leukocyte culture interaction.

Animals↗
PubMed2006

Regulation of PTEN function as a PIP3 gatekeeper through membrane interaction.

PTEN, one of the most frequently mutated genes in human cancer, acts as a tumor suppressor by dephosphorylating the plasma membrane lipid second messenger phosphoinositide-3,4,5-trisphosphate (PIP3) generated by the action of PI3Kinases. PTEN activity to prevent elevated levels of PIP3 and tumorigenesis depends on its interaction with the lipid bilayer. PTEN binds dynamically to the plasma membrane through a complex mix of protein-lipid and protein-protein interactions and the translocation is regulated by several mechanisms including C-terminal tail phosphorylations. Here we have summarized our current view of the interaction of PTEN with the plasma membrane and what the implications are for cancer biology.

Cell Membrane↗
PubMed2003

Ageism in the management of lung cancer.

BACKGROUND: age-related differences in the treatment of lung cancer patients have been reported in the past, but most previous studies have not recorded case-mix factors, nor have they studied the impact of such ageism on survival. METHODS: a questionnaire-based study of diagnostic and case-mix factors was carried out across 48 hospital Trusts in the UK between 1997 and 1998. We identified 1,652 patients and followed through with regard to their treatment and survival for 6 months after diagnosis. RESULTS: the median age of the population was 69 years, and for this analysis, was divided into three age groups: under 65 years, 65-74 and 75 years and over. There were significant inverse correlations between age and histological diagnosis, any active treatment and survival, even when corrected for case-mix factors and non-cancer causes of death. For example, the surgical resection rate in patients with confirmed non-small cell lung cancer with good performance status, no chronic obstructive pulmonary disease and limited disease was 37% in the younger patients compared with 15% in those 75 and over. The overall mortality rates at 6 months ranged from 42% in patients under 65 to 58% in the over 75s. CONCLUSIONS: this national study of lung cancer care in the UK has shown large age-related differences in management and survival in patients with lung cancer, largely independent of case-mix factors. The reasons for this are complex but such under-treatment in the elderly may be one factor underlying the poor outcomes in lung cancer patients in the UK.

Adult↗
PubMed1986

Cartilage-cell-containing tumours of the pelvis: a radiological review of 40 patients.

Cartilage-cell-containing tumours of the pelvis are responsible for a quarter of all primary bone lesions in this site. Benign tumours are uncommon but when present have classical radiological appearances similar to those described elsewhere. Only the rarest, chondromyxoid fibroma, may cause difficulty in diagnosis. Seventy-three per cent of cartilage-cell tumours are malignant and are either chondrosarcoma or chondroblastic osteosarcoma. Chondrosarcoma occurs after the second decade of life, usually with a longer history, and may be categorised as either a secondary peripheral or primary central tumour, each having typical radiological features. Chrondroblastic osteosarcoma tends to occur in younger patients with a shorter clinical history and is almost exclusively situated adjacent to a sacroiliac joint, producing purely lytic, sclerotic or mixed patterns of bone destruction. Experience suggests that computed tomography is the single most valuable further examination, since the pelvis is a complex structure with confusing overlying soft-tissue artefacts. This technique may indicate both the route and choice of optimal biopsy site.

Adolescent↗
PubMed2002

Immunolocalization of the smooth muscle-specific protein calponin in complex and mixed tumors of the mammary gland of the dog: assessment of the morphogenetic role of the myoepithelium.

The immunohistochemical expression of the smooth muscle-specific protein calponin was studied to assess the contribution of myoepithelial cells to the histogenesis of spindle cells of complex and mixed tumors of the mammary gland of the dog and the origin of cartilage and bone in mixed tumors. Formalin-fixed tissues from 55 benign and malignant tumors (49 also containing surrounding normal mammary gland) were evaluated. Periacinar and periductal myoepithelial cells of all the 49 normal mammary glands were diffusely stained by the anti-human calponin monoclonal antibody. Calponin was found in 53 (98%) of the tumors studied, reacting with the myoepithelium-like cells of 86% of benign tumors and their remnants in 85% of malignant tumors. Five different types of calponin-immunoreactive myoepithelial cells were identified: hypertrophic myoepithelial cells. fusiform cells, stellate myoepithelial cells, rounded (myoepithelial) cells, and chondroblasts. Differences in staining intensity and staining pattern among these five types of cells suggested a transition of myoepithelial cells to chondroblasts. Stromal myofibroblasts also showed calponin immunoreactivity, but they did not react with a cytokeratin 14 monoclonal antibody, which recognizes myoepithelial cells in mammary gland. Calponin appears to be a very sensitive marker of normal and neoplastic myoepithelium in the canine mammary gland, and its identification in different cell types of complex and mixed tumors of the mammary gland of the dog suggests a major histogenetic role for myoepithelial cells.

Animals↗
PubMed1975

Immune reactivity in vitro to spontaneous canine oral tumors.

In vitro reactivity of autochthonous lymphocytes to tumor cells from progressively growing oral tumors in dogs was studied. Tumors were collected during surgery or before necropsy and prepared for tissue culture. Only viable, glass-adherent tumor cells were used. The cells were first incubated either with culture medium or with canine serum, and then they were mixed with lymphocytes. The cultured tumor cells were destroyed by high numbers of lymphocytes, but the reactivity was blocked for tumor cells that had been incubated with autologous serum. Tumor cell growth was stimulated by low numbers of lymphocytes. These results point out the complexity of tumor enhancement in vivo.

Animals↗
PubMed2004

Spectrum of malignant lymphomas in Bahrain. Leitmotif of a regional pattern.

OBJECTIVE: To determine the clinicopathologic features of malignant lymphomas in Bahraini patients. METHODS: A retrospective hospital-based study was conducted. All new cases of malignant lymphoma diagnosed during the period January 1996 to December 2001 at the Salmaniya Medical Complex in Bahrain were included in the study. RESULTS: Seventy-two cases met the inclusion criteria. This included 24 (33.3%) cases of Hodgkin's disease (HD) and 48 (66.7%) cases of Non-Hodgkin lymphomas (NHL). A young age at presentation (median 20 years) mixed cellularity histology, lack of extra nodal involvement and rare marrow involvement characterized HD. The majority of NHL showed diffuse high or intermediate grade lesions. A high number of primary extra nodal neoplasms (41.7% of NHL) and frequent involvement of the gastrointestinal tract with Helicobacter pylori-associated gastric lymphomas were notable features among NHL cases. Immunohistochemical staining in 30 cases showed 26 cases (86.7%) of B cell and 4 cases of T cell origin. CONCLUSION: The study highlights common features that distinguish malignant lymphoma reported from countries of the Arabian Gulf region. This pattern distinguishes them from the disease encountered in the Western world.

Adolescent↗
PubMed1990

[Radiographic study of odontomas].

Odontomas are the most common benign odontogenic tumors with a high degree of differentiation and an excellent biological behavior. Three histological types are recognised: a) ameloblastic odontoma, b) coplex odontoma and c) compound odontoma. Usually these tumors are asymptomatic and the most frequent cause of discovery is the retention or impaction of a permanent tooth. The purpose of this study was to analyze the clinical and radiographic features of these tumors and to determine the frequency and relation of odontomas to tooth impaction. Twenty six cases (14 males and 12 females) of histologically verified odontomas were studied and an effort was made in order to corellate the histological type of the tumors with the age, the sex, the location, the radiographic picture, the size of the lesion and the frequency and relation to the impacted teeth. The main conclusions of the study were: a) Odontomas are diagnosed more often in the first or second decade but the compound odontoma may be seen later in life. b) The most common location of odontomas is the anterior region of the maxilla, c) The radiographic picture of the complex odontoma is usually of the mixed radiolucent-radiopaque type, where compound odontoma is more often found as radiopacity or as non-typical tooth and d) Odontomas more often are located above the crown of the impacted tooth usually in maxillary incisors and canines.

Adolescent↗
PubMed1993

Pathology of temporal lobectomy for refractory seizures in children. Review of 20 cases including some unique malformative lesions.

Significant pathological abnormalities were encountered in a series of 20 temporal lobectomies in children with intractable complex partial seizures. In particular, "dual pathology" (mesial temporal sclerosis with other lesions) was found rather than mesial temporal sclerosis as the only lesion. Unusual pathological findings included capillary penetration of neurons in a neuronal heterotopia in one patient, and foci of extensive cortical disorganization in some cases of mixed tumors and gangliogliomas. A high proportion of neuronal migration disorders was also seen with overlapping pathological features between cortical dysplasia and tuberous sclerosis. In this correlative clinical, radiological, electroencephalographic, and pathological study, some of the pathological lesions in children did not fit the classical categories of neoplasia and malformation and transitional forms were rarely encountered.

Adolescent↗
PubMed2000

Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse.

We have selected a well-characterized human renal cell carcinoma (RCC) line as the basis for development of a genetically engineered tumor cell vaccine to be applied in an allogeneic setting. This cell line was genetically modified by retroviral transduction to express B7.1 costimulatory molecules. The unmodified tumor cells and B7.1-expressing tumor cells were compared for their ability to induce tumor-associated responses in allogeneic peripheral blood mononuclear cells (PBMC) of two normal control donors having single MHC class I allele matches with the tumor cells. PBMC primed using B7.1-modified tumor cells showed a preponderance of CD3+CD8+ cytotoxic T lymphocytes (CTL) that proliferated over extended periods of time in mixed lymphocyte tumor cell (MLTC) cultures. Strong cytolytic activity developed in the primed populations and included allospecific CTL with specificity for mismatched HLA-A, -B and -C molecules. Nevertheless, it was possible to isolate CTL clones that were able to lyse tumor cells but not lymphoblastoid cells that expressed all the corresponding allospecificities. Thus, induction of complex allospecific responses did not hinder the development of tumor-associated CTL in vitro. These results support the use of this genetically modified allogeneic tumor cell line for vaccination of partial-MHC matched RCC patients.

B7-1 Antigen↗
PubMed1984

Myosin and myoglobin as tumor markers in the diagnosis of rhabdomyosarcoma. A comparative study.

Antibodies against the myosin heavy chain of adult chicken pectoral muscle and heart muscle which cross-react with myosin of human fast type II fibers ( antifast myosin) and slow type I fibers ( antislow myosin), respectively, and antibodies against human myoglobin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Formaldehyde-fixed and paraffin-embedded tissue and the avidin-biotinyl-peroxidase complex technique were used. Of 23 rhabdomyosarcomas studied, 20 were positive with antifast myosin and 11 with antimyoglobin . All tumors were negative with antislow myosin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic, regardless of the antiserum used. Staining with antimyoglobin was generally limited to the cytoplasm-rich tumor cells. Besides rhabdomyosarcomas, the only other positive neoplasms were those which contained rhabdomyoblastic differentiation such as malignant Triton tumors and malignant mixed müllerian tumors. Our results indicate that antibodies against the fast myosin heavy chain are a useful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish that tumor from other small round cell tumors in childhood. The results are discussed in the light of the embryogenesis of skeletal muscle.

Adolescent↗
PubMed1980

Lipoblastic tumours of somatic soft tissues: a xerographic evaluation of 67 cases.

The role of xeroradiography for the diagnosis and the clinical evaluation of lipoblastic tumours of somatic soft tissues was investigated in 67 patients. Xeroradiography improved the visibility of soft tissues over film radiography in 20 out of the 23 cases in which both examinations were performed. The xeroradiographic characters of a lipoblastic tumour depend on its nature, thus irregular and infiltrative masses are usually liposarcomas, while regular and rounded nodes are usually pure or mixed lipomas. Moreover, pure lipomas are always radiolucent and liposarcomas are always radiopaque. Xeroradiography is regarded as a promising first technique in the diagnosis of lipoblastic tumours, before more complex investigations, like computed tomography (CT) scanning or arteriography, are undertaken.

Evaluation Studies as Topic↗
PubMed1999

The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function.

We compared the oestrogenic and anti-oestrogenic properties of the two well-known phyto-oestrogens, genistein and quercetin, on the oestrogen-sensitive breast cancer cell line MCF-7. Genistein exerted a biphasic effect on growth of MCF-7 cells, stimulating at low and inhibiting at high concentrations, whereas quercetin was only growth inhibitory. At doses which did not inhibit cell growth, respectively 5 and 1 microM, genistein and quercetin counteracted oestrogen- and transforming growth factor-alpha-promoted cell growth stimulation. Furthermore, genistein promoted transcription of the oestrogen-regulated genes pS2 and cathepsin-D, whereas quercetin interfered with the oestrogen-induced expression of the proteins. In in vitro binding experiments, genistein competed with oestradiol for binding to the oestrogen receptor (ER), but quercetin did not. Quercetin and genistein down-regulated cytoplasmic ER levels and promoted a tighter nuclear association of the ER, but only genistein was able to up-regulate progesterone receptor protein levels. In gel mobility assays, ER preincubation with oestradiol or with the two phyto-oestrogens led to the appearance of the same retarded band, excluding differences between the various complexes in binding to the consensus sequence. The data allowed us to conclude that quercetin acts like a pure anti-oestrogen, whereas genistein displays mixed agonist/antagonist properties, and to formulate a hypothesis on the possible mechanism of action of such phyto-oestrogens.

Amino Acid Sequence↗
PubMed2002

Cutting edge: CD83 regulates the development of cellular immunity.

We recently found that human CD83, a marker of mature dendritic cells, is an adhesion receptor that binds to resting monocytes and a subset of activated CD8(+) T cells. We injected CD83-Ig into mice transplanted with the immunogenic P815 mastocytoma and showed that it significantly enhanced the rate of tumor growth and inhibited the development of cytotoxic T cells. In contrast, mice immunized with CD83-transfected K1735 cells, a poorly immunogenic melanoma, could prevent the outgrowth of wild-type K1735 cells. Studies performed in vitro with human PBL showed that coimmobilized CD83-Ig and anti-CD3 enhanced T cell proliferation and increased the proportion of CD8(+) T cells. CD83-transfected B-lymphoblastoid T51 cells stimulated T cell proliferation more effectively than untransfected T51 cells in MLR cultures and increased the generation of cytolytic T cells. We conclude that CD83 is a functionally important receptor that can regulate the development of cellular immunity by interacting with its ligand(s).

Animals↗
PubMed2002

Detection of human polyomaviruses and papillomaviruses in prostatic tissue reveals the prostate as a habitat for multiple viral infections.

BACKGROUND: To determine whether human polyomavirus (hPy) genomes are present in prostate tissues, we have carried out a polymerase chain reaction (PCR) screening in two sets of prostate samples, archival and fresh frozen, as well as performing in situ hybridization (ISH). The frozen prostate samples as well as the urine from the same patients were also screened for human papillomavirus (HPV) sequences. METHODS: Highly sensitive nested-PCR assays were used. The detection of subpopulations of JC virus (JCV) -transcriptional control regions (TCRs) was also evaluated by Southern analysis and by direct DNA sequencing. An in situ hybridization technique was also used to detect JCV DNA in prostatic tissue. RESULTS: The paraffin-embedded archival samples gave variable, unsatisfactory results. Results from the fresh frozen samples, however, were consistent and were frequently positive for JCV and less frequent for BK virus DNA. ISH confirmed the presence of JCV DNA in prostatic glandular epithelium. The TCR region of JCV from prostate tissue and urine from prostate cancer patients showed the presence of both archetypal and rearranged TCRs, including several new sequence variants. HPV DNA was also frequently detected and in some cases also mixed with hPy DNA from frozen tissue and urine. CONCLUSION: The use of fresh frozen samples proved to be essential for consistent and reproducible detection of HPV and hPy viral DNAs. The presence of JCV DNA by ISH and the occurrence of a subpopulation of JCV TCR regions suggests that the prostate is a site for virus replication. The prostate is a complex habitat where mixed infections with oncogenic DNA viruses frequently occur and opens the discussion to the potential role of these viruses in the cancer of the prostate.

Aged↗
PubMed2005

Parents' assessment of risk in sickle cell disease treatment with hydroxyurea.

Hydroxyurea is the only medication shown to reduce the severity of sickle cell disease (SCD), but its long-term risks are unknown. Families of 58 children with SCD were interviewed on their perception of the potential risks of hydroxyurea treatment, and whether disease severity was a major factor in their treatment decision. Parents rated the severity of their child's SCD (86% as severe, 26% moderate, and 47% mild) and then the highest levels of risk that they would tolerate for both potential cancer (range 1/1,000 to 1/2) and potential birth defects (range 1/1,000 to 1/3) to benefit their child with hypothetical hydroxyurea treatment. Parents of 29 of the 58 children were unwilling to take any cancer risk whatsoever as a potential side effect of treatment, and 29 of 58 (not all the same parents) were unwilling to take any risk for birth defects, including half the children with severe SCD. For those families who did accept some risk, higher acceptable risk correlated with higher disease severity in the child (P = 0.04). The study's mixed findings highlight the complexities of risk perception and suggest that future studies of risks and benefits from the parental viewpoint are needed as candidate therapies are developed for SCD.

Abnormalities, Drug-Induced↗