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Results for “Neoplasms, Complex and Mixed”

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PubMed2001

Synthesis and preliminary evaluation of Tc-99m-labeled somatostatin analog (RC-160) using "3+1" mixed ligand approach.

The success of (111)In-pentetreotide as a cancer-imaging agent has given impetus to the search for other peptide-based radiopharmaceuticals. The labeling with Tc-99m has become even more attractive because of the ready availability and near ideal physical properties. Additionally, the kinetics of the peptide-receptor interactions favors the radiolabeling with technetium-99m. A somatostatin analog RC-160 has been labeled with Tc-99m using the "3+1" mixed ligand approach utilizing the NNS/S coordination sites. The ternary complex was formed in greater than 95% within 30 min by simultaneous reduction and complexation of technetium-99m pertechnetate. The Tc-99m and the surrogate rhenium complexes showed similar chromatographic behavior. The complex was evaluated by in vitro receptor binding studies carried out on HTB-121 breast cancer cell line and biodistribution studies performed in normal mice. Our findings suggest that RC-160 can be labeled by the mixed ligand approach with the complex retaining its biological activity and warrants further studies.

Animals↗

PubMed1994

Plutonium-induced proliferative lesions and pulmonary epithelial neoplasms in the rat: immunohistochemical and ultrastructural evidence for their origin from type II pneumocytes.

Immunohistochemistry and transmission electron microscopy were used to clarify the cellular origin for plutonium-239-induced pulmonary proliferative (preneoplastic) epithelial lesions and epithelial neoplasms in F344 rats. Examples of each histologic type of proliferative lesion and neoplasm were stained by the avidin-biotin complex immunoperoxidase method using antibodies to rat surfactant apoprotein and Clara cell antigen. Rat surfactant apoprotein immunostaining was detected in type II pneumocytes in sections of normal lung, in the cells of the proliferative lesions classified histologically as alveolar epithelial hyperplasia (51) and mixed foci (alveolar epithelial hyperplasia with fibrosis) (30), and in adenomas (2), adenocarcinomas (3), and adenosquamous carcinomas (2). With the exception of one adenosquamous carcinoma, Clara cell antigen immunostaining was not detected in any of the pulmonary lesions but was detected in nonciliated cuboidal epithelial (Clara) cells in normal bronchioles. The epithelial cells of the proliferative lesions and neoplasms had ultrastructural features consistent with type II pneumocytes, i.e., the presence of cytoplasmic lamellar and multivesicular bodies. The results of these studies indicate that the majority of plutonium-induced proliferative epithelial lesions and neoplasms in the rat originate from alveolar type II pneumocytes.

Animals↗

PubMed1993

An autoreactive T cell clone generated in the autologous mixed lymphocyte reaction in a patient with gastric carcinoma.

Autoreactive T cell clones were established from a patient with early gastric carcinoma and a healthy control in order to investigate the mechanism of suppression of autologous mixed lymphocyte reaction (AMLR) and its significance in immune surveillance against tumor. Clone 3F6 from the gastric carcinoma patient responded to only autologous non-T cells with less reactivity than 4 clones from the control subject. The proliferative response of clone 3F6 to interleukin-2 and immobilized anti-CD3 antibody was also suppressed when compared with the control clones. Autoreactive T cells were able to kill tumor cells and autologous PHA-blasts. The cytotoxic activity of clone 3F6 was also markedly suppressed when compared with the control clones. This data suggests that autoreactive T cells may be impaired in cancer patients and that this immunological disorder might cause the defective immune surveillance against tumors.

Autoimmunity↗

PubMed1983

Interaction of filipin with junctional membrane at different stages of the junction's life history.

The relationship of filipin-sterol complexes to tight and gap junctions during their formation, maturation, internalization, and degradation was studied in separate cell lines. Filipin-sterol complexes tended to be excluded from mature junctions in tight junction forming COLO 316 cells and gap junction forming SW-13 cells. Once internalized, unlabeled junctional membrane appeared to fuse with heavily labeled vesicles, presumably lysosomes. Although the absence of filipin-sterol complexes from junctional membrane does not necessarily reflect the absolute sterol content of this membrane, the fact that filipin-sterol complexes are largely excluded from these areas indicates that this membrane is different from surrounding membrane. The absence of filipin-sterol complexes also permits the visualization of 'mixing' of this specialized unlabeled membrane domain with other filipin labeled membrane systems.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Modifying effect of organocobalt complexes on the tumour response to anticancer treatments.

A new type of agents are proposed for combined cancer therapy. They are organocobalt (III) chelates containing a sigma-bounded organyl group and a mixed tridentate ligand derived from a Schiff base. These complexes generate free radicals due to the action of protons in physiological ranges of pH and temperature, and hence are conceivably capable of selectively attacking a malignant neoplasm that is slightly acidic and can be made even more so by introducing some means intensifying glycolysis. An in vivo examination was performed using transplanted rat tumours (Guerin and Walker 256 carcinomas, Sarcoma 45). The modifying effect of one of these complexes on the tumour response to cis-DDP, radiation and/or local hyperthermia was tested by means of tumour growth delay assay and local tumour control. The potentiating effect of the complex was maximal when it was administered 60-90 minutes prior to other agents (cisDDP, X-irradiation heat). The enhancement ratio was found to be ca. 2.0-4.0 for cisDDP and 2.0 for radiation. In conclusion, in our tumour models, an increase of the antitumour effect was obtained for conventional antitumour agents when they were supplemented with organocobalt complex. It can be hypothesised that DNA in tumour cells may be considered to be the main target for organocobalt complexes.

Animals↗

PubMed2006

A tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes.

We recently reported on newly designed virus-targeted bispecific CD3- and CD28-binding molecules for human T-cell activation. When bound via one arm to a human virus-modified tumor cell vaccine, these reagents caused a polyclonal T-cell response and overcame the potential various T-cell evasion mechanisms of tumor cells. In our current study, we demonstrated the induction of strong antitumor activity in human lymphocytes upon coincubation with a virus-modified tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies. Blood mononuclear cells or purified T cells that were coincubated with such a tumor vaccine for 3 days were able to destroy monolayers of human breast carcinoma and other carcinoma cells. Serial transfer to new tumor cell monolayers revealed antitumor cytotoxic activity in such effector cells that lasted for about 10 days. Nontumor target cells appeared to be much less sensitive to the activated effector cells. Although the bispecific molecules alone did not activate effector cells, their binding to virus-infected tumor cells was important and more effective than their binding to free virus. Antitumor activity of the activated effector cells was mediated through soluble factors as well as through direct cell contact of effector cells with the nontargeted bystander tumor cells. Since the virus-modified tumor vaccine is well tolerated and already exhibits a certain effectiveness in cancer patients, the combination with new bispecific molecules has the potential to introduce additional antitumor effects. The reagents can also be combined with Newcastle Disease Virus (NDV)-based oncolytic virotherapy.

Antibodies, Bispecific↗

PubMed1992

18O isotopic 13C NMR shift as proof that bifunctional peptidylglycine alpha-amidating enzyme is a monooxygenase.

The biosynthesis of C-terminal alpha-amidated peptides from their corresponding C-terminal glycine-extended precursors is catalyzed by peptidylglycine alpha-amidating enzyme (alpha-AE) in a reaction that requires copper, ascorbate, and molecular oxygen. Using bifunctional type A rat alpha-AE, we have shown that O2 is the source of the alpha-carbonyl oxygen of pyruvate produced during the amidation of dansyl-Tyr-Val-[alpha-13C]-D-Ala, as demonstrated by the 18O isotopic shift in the 13C NMR spectrum of [alpha-13C]lactate generated from [alpha-13C]pyruvate in the presence of lactate dehydrogenase and NADH. In addition, one-to-one stoichiometries have been determined for glyoxylate formed/dansyl-Tyr-Val-Gly consumed, pyruvate formed/dansyl-Tyr-Val-D-Ala consumed, dansyl-Tyr-Val-NH2 formed/ascorbate oxidized, and dansyl-Tyr-Val-NH2 formed/O2 consumed. Quantitative coupling of NADH oxidation to dansyl-Tyr-Val-NH2 production using Neurospora crassa semidehydroascorbate reductase showed that two one-electron reductions by ascorbate occurred per alpha-AE turnover. The stoichiometry of approximately 1.0 dansyl-Tyr-Val-NH2 produced/ascorbate oxidized observed in the absence of a semidehydroascorbate trap resulted from the disproportionation of two semidehydroascorbate molecules to ascorbate and dehydroascorbate.

Amino Acid Sequence↗

PubMed1978

Human-mouse mixed lymphocyte cultures.

Conditions for stimulating human lymphocytes with mouse cells are established. The proliferative and cytotoxic responses generated are shown to be specific for antigens coded for in the major histocompatibility locus.

Animals↗

PubMedDate not supplied

Macrochimerism of donor type CD56+ CD3+ T cells in donor specific transfusion via portal vein following living related donor liver transplantation.

Antigens given orally or through the portal vein are known to be less immunogenic and to induce immunologic unresponsiveness. The mechanisms responsible for graft enhancement are still unclear. Moreover, in actuality, it is difficult to perform transfer of donor antigens via the portal vein in clinical transplantation. We investigated the effect of transfer of donor blood via the portal vein intra- and post-operatively in living related donor liver transplantation for recurrent multiple hepatocellular carcinoma. A 62-year-old female, who suffered from recurrent multiple hepatocellular carcinoma with hepatitis C virus, underwent living related donor liver transplantation with the right lobe of her daughter. Eleven hepatocellular carcinomas were recognized in the resected specimen. Donor blood was administered via the portal vein using a catheter inserted in the middle colic vein intra- and postoperatively. Mononuclear cells were obtained by operative liver biopsy or postoperative biopsy using fine needle aspiration biopsy, and from peripheral blood. They were analyzed by two or three color-flow cytometry using several antibodies. The differentiation between donor and recipient was estimated by means of anti-HLA antibodies of donor and recipient. The postoperative course was uneventful. She did not suffer from acute cellular rejection and was discharged on day 30 the after operation. CD56+ CD3+ T cells in the liver increased notably from 20% to 50% after transplantation. One half of the CD56+ CD3+ T cells in the liver graft were of the donor type (donor anti-HLA A2 antibody) on day 8 after surgery. Donor type CD56+ CD3+ T cells occupied 17.4% of the total CD56+ CD3+ T cells even on day 42 after the operation. Stimulation index by mixed lymphocyte reaction continued at a low level (< 2) from day 1 after the operation. Steroids were discontinued after 40 postoperative days. FK506 was also reduced to 0.5 mg/day 4 months after the operation. There was no recurrence of hepatocellular carcinoma and hepatitis C virus for two years after the operation. Macrochimerism of donor type CD56+ CD3+ T cells in a graft might be induced by the transfer of donor blood via the portal vein and may play an important role in transplantation tolerance. Inoculation of donor blood via the portal vein may also be very useful for rapid reduction of immunosuppression.

Blood Transfusion↗

PubMed1985

Coexpression of intermediate filaments in human epithelial neoplasms.

A wide variety of human neoplasms were examined by immunocytochemical and ultrastructural techniques. In most, one intermediate filament (IF) type was expressed reflecting the tissue of origin. However, multiple classes of intermediate filaments were regularly found in a subgroup of these tumors. We chose to subdivide them into those with a complex or mixed growth pattern, and those which showed a more "monomorphic" histologic growth pattern. This latter group is the subject of this paper. Regular coexpression of cytokeratin and vimentin was observed in tumors of endometrial, thyroid, ovarian and renal origin, and coexpression of cytokeratin and neurofilament was observed in a subgroup of neuroendocrine tumors. Immunocytochemical/ultrastructural correlation demonstrated few, if any, observable intermediate filaments in tumors expressing only low molecular weight cytokeratin, whereas vimentin and neural filament characteristically were randomly dispersed or formed whorled bundles of cytoplasmic filaments. The potential diagnostic usefulness of these observations in surgical pathology is discussed.

Carcinoid Tumor↗

PubMed1994

Biochemical pharmacology of homologous alicyclic mixed amine platinum(II) complexes in sensitive and resistant tumor cell lines.

Three homologous alicyclic mixed amine cis-(NH3)(R-NH2)Cl2Pt(II) complexes, in which R = C3H5, C6H11, and C8H15 (complexes abbreviated C3, C6, and C8, respectively), were evaluated with reference compounds cisplatin and tetraplatin for antitumor activities and biochemical pharmacology in wild-type (murine leukemia L1210/0 and human ovarian A2780) and corresponding variant cell lines resistant to cisplatin (L1210/DDP and 2780CP) and tetraplatin (L1210/DACH and 2780TP). Cytotoxicities, measured by either a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or a clonogenic assay, were maximal for the C6 complex, which was up to 12-, 40-, and 6-fold more potent than C3 against wild-type, cisplatin-resistant, and tetraplatin-resistant models, respectively, and up to 2-fold more potent than C8 against these cell lines. In general, cross-resistance to mixed amine analogues was partial in cisplatin- and tetraplatin-resistant cells and decreased (in L1210/DDP and 2780CP) or increased (in L1210/DACH and 2780TP) with increase in the alicyclic ring size. The increase in ring size resulted in a corresponding increase in partition coefficient, which correlated directly with intracellular accumulations of mixed amine analogues in all cell lines. However, the intracellular DNA-platinum adducts, and not cellular platinum content, was the pharmacological entity that corresponded closely to potencies of the molecules. DNA adduct formation was disproportionate to the level of cellular drug accumulation. For instance, complex C8, which accumulated to the greatest extent in any given cell line, produced adduct levels that were similar to or lower than those produced by C6. A partial explanation for this observation was the demonstrated reduced rate of binding of C8 to DNA. This study has highlighted the significance of alicyclic ring size in modulating the potency, cross-resistance profile, and biochemical pharmacology of mixed amine platinum(II) complexes in sensitive and cisplatin- or tetraplatin-resistant tumor cells.

Animals↗

PubMed1974

Inhibition of tumor-induced lymphocyte blastogenesis by a factor or factors associated with peripheral leukocytes.

A factor or factors concentrated on leukocytes of cancer patients depress the proliferative response of lymphocytes to stimulation with autologous tumor. Inhibitory activity with material eluted from cells resides in neither high nor lower molecular weight fractions but in a combination of the two. The finding suggests that in vitro inhibition of lymphocyte proliferation to autochthonous tumor occurs because of antigen-antibody complexes.

Adenocarcinoma↗

PubMed1993

Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas.

In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CD11 negative cells in a CD3 positive subpopulation.

Antigens, Surface↗

PubMed2004

Microdissection genotyping of mixed glial and primitive neuroectodermal central nervous system neoplasm.

A 22-year-old man with previous radiation treatment for childhood astrocytoma underwent resection of a right parietooccipital lesion. Histopathology revealed a malignant neoplasm with areas of astrocytic and primitive neuroectodermal components. To resolve the relationship and cellular origin, representative tissue was microdissected from several targets, obtaining a balanced mixture of each element. Nonneoplastic brain parenchyma was separately microdissected to determine polymorphic marker informativeness and to serve as an internal negative control. Despite the relatively small quantity of tissue removed for each microdissection target, sufficient material was available for reliable, balanced, polymerase chain reaction-format genotyping encompassing a panel of tumor suppressor genes and genetic loci associated with these forms of neoplasia. The findings revealed distinct discordant genotypic profiles for each of the neoplastic components. The efficacy of the approach used for molecular analysis of this complex neoplasm and the implication of the genotypic findings are discussed.

Adult↗

PubMed1990

Composite mucinous and granulosa-cell tumor of ovary: case report of a unique neoplasm.

A 63-year-old woman presented with signs and symptoms of an estrogen-producing ovarian tumor. At laparotomy, this tumor proved to be a multilocular right ovarian mass 20 cm in greatest diameter. The cystic spaces were lined by typical benign mucinous epithelium of the endocervical type, while the greatly thickened cyst walls contained a diffuse proliferation of granulosa cells. These two disparate components were intimately mixed at a variably complex interface to form a composite tumor. While composite tumors showing sex cord-stromal and epithelial elements are well documented, they have all, to date, been of moderately to poorly differentiated androblastomatous or Sertoli-Leydig cell type, associated with heterologous mucinous elements of intestinal differentiation. The combination of granulosa-cell tumor with mucinous elements of endocervical or müllerian type has not hitherto been reported and is of uncertain histogenesis.

Adenocarcinoma, Mucinous↗

PubMed1988

Structure-activity relationships for glycine-extended peptides and the alpha-amidating enzyme derived from medullary thyroid CA-77 cells.

A peptidyl alpha-amidating enzyme has been partially purified from conditioned medium derived from cultured medullary thyroid CA-77 cells. The interactions of this enzyme with a series of tripeptides, pentapeptides, and mature glycine-extended prohormones has now been studied using a competition assay that features the enzymatic alpha-amidation of N-dansyl-Tyr-Val-Gly. While a peptide C-terminal glycine was obligatory for tight binding to the alpha-amidating enzyme, other peptide structural elements modulated the interaction. Thus, a greater than 1300-fold range in apparent inhibitor constants was observed by substitution at the -1 (penultimate) position in a C-terminal glycine-containing tripeptide with each of the 20 common L-amino acids. Peptide inhibitory potency decreased through the following amino acid groupings: sulfur containing greater than aromatic greater than or equal to histidine greater than nonpolar greater than polar greater than glycine greater than charged. This pattern was qualitatively dissimilar to that observed for a more limited series of substitutions at the -2 position, demonstrating the positional selectivity of these structural requirements. The structure-activity relationships observed with the tripeptides at the -1 position were consistent with the apparent inhibitor constants obtained for a collection of prohormones and their pentapeptide mimics. Finally, selected prohormones and their pentapeptide mimics were equipotent inhibitors, demonstrating that the peptide structural elements important for alpha-amidating enzyme recognition are located entirely within the C-terminal pentapeptide segment.

Animals↗

PubMedDate not supplied

Immunohistochemical characterization of cancer antigen in uterine cancers.

The pattern of cancer antigen (CA-125) expression by immunohistochemistry (IHC) was investigated in malignant and nonneoplastic endometrium in endometrial carcinoma. Ninety cases of primary uterine carcinomas (65 endometrioid [EM] carcinoma, 15 serous papillary [SP] carcinoma, 6 carcinosarcomas [malignant mixed müllerian tumors], and 4 clear cell carcinoma [CC]) and adjacent atrophic and/or hyperplastic endometrium were analyzed by IHC for CA-125 expression. The percentage and intensity of luminal, apical, basal, and diffuse cytoplasmic immunostaining of epithelial cells were categorized on a scale of 0-4. The immunoreaction score (IRS score) was calculated and correlated with the grade and stage of carcinoma according to the histologic type. CA-125 expression (3-4/4) was localized in apical borders of grade 1 and grade 2 EM carcinoma and was weak or negative (0-1/4) in grade 3 EM. Mucinous differentiation in EM was associated with intense luminal and apical staining. Squamous areas and stroma showed no staining at all. SP carcinoma and endometrial intraepithelial carcinoma showed much higher mean IRS score than EM. In malignant mixed müllerian tumors (MMMT), the epithelial component stained as above according to the type of epithelial cell differentiation of the neoplastic cells. Benign proliferative glands showed moderate apical luminal, basal, and cytoplasmic staining. Intense diffuse staining was observed in atypical complex hyperplasia. Different patterns of CA-125 immunostaining were observed in normal, hyperplastic, and neoplastic endometrium. IRS score correlated with the grade but not with the stage of EM carcinoma. The intense different staining pattern of endometrium with atypical complex hyperplasia suggests that CA-125 may be a useful diagnostic aid.

Adenocarcinoma↗

PubMed1995

Immunophenotypic characterization of cutaneous lymphoid neoplasia in the dog and cat.

Clinical, histopathological and immunohistochemical findings are presented from a series of cutaneous lymphoid neoplasms including canine epitheliotrophic lymphoma (n = 7), canine non-epitheliotrophic cutaneous lymphoma (n = 10), canine cutaneous plasmacytoma (n = 10) and feline non-epitheliotrophic cutaneous lymphoma (n = 6). Three cases of canine epitheliotrophic lymphoma expressed the CD3 T-lymphocyte marker, but the remainder were negative for this molecule and for a panel of B-cell markers. Non-epitheliotrophic cutaneous lymphoma was shown to be predominantly of T-cell phenotype (CD3+) in the dog (eight of 10 cases) and cat (five of six cases), the remaining cases in both species being of B-cell origin, expressing the gamma heavy chain of immunoglobulin (with or without lambda light chain). One canine non-epitheliotrophic B-cell lymphoma expressed IgG of the IgG2 subclass. Two of the biopsies from dogs with cutaneous plasmacotyoma were shown to express immunoglobulin alpha chain (one with lambda chain) and two neoplasms were positive for immunoglobulin gamma chain (both with lambda chain). One of the latter immunoglobulins was of the IgG4 subclass. In the majority of all cases of cutaneous lymphoid neoplasia examined, there was a local polyclonal immune response, manifested as infiltration by a mixed population of plasma cells expressing IgG (IgG2, IgG4), IgA or IgM. In the feline tumours CD3+ small T lymphocytes were included in these infiltrates.

Animals↗