Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites.

The locations of distant secondary tumors in many clinical cancers and animal tumors are nonrandom, and their distributions cannot be explained by simple anatomical or mechanical hypotheses based on the simple lodgment or trapping of tumor cell emboli in the first capillary bed encountered. Evidence from certain experimental tumor systems supports Paget's 'seed and soil' hypothesis on the nonrandom distributions of metastases, in which the unique properties of particular tumor cells ('seeds') and the different characteristics of each organ microenvironment ('soil') collectively determine the organ preference of metastasis. Experimentally, differential tumor cell adhesion to organ-derived microvessel endothelial cells and organ parenchymal cells, differential invasion of basement membranes and organ tissues, and differential responses to organ-derived growth-stimulatory and -inhibitory factors all appear to be important determinants in explaining the organ preference of metastasis.

Bcl-1 gene rearrangements in B cell lymphoma.

We analyzed 50 B cell lymphoma samples by Southern blot analysis, using the bcl-1 and heavy chain immunoglobulin (JH) probes with two or more restriction endonucleases. All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences. The three samples showed the t(11;14)(q13;q32) chromosome translocation, and all three contained rearranged JH fragments that comigrated with the rearranged bcl-1 fragment.

Atrophy with compensatory hypertrophy of the liver in hepatic neoplasms: radiographic findings.

Focal hepatic atrophy has numerous causes and in many cases is associated with compensatory hypertrophy. We have observed this phenomenon on CT in patients with hepatic neoplasms. Of 12 patients studied, eight had hepatic metastases, two had hepatocellular carcinoma, and two had bile-duct carcinoma.

In vitro activity of amonafide against primary human tumors compared with the activity of standard agents.

Amonafide, one of a series of benz[de]-isoquinoline-1,3-dione compounds, is now entering phase II clinical trials in this country. We tested amonafide, exposed continuously for 5 days, at four different concentrations against 56 primary human tumors in vitro. The drug concentration range used was based on amonafide's inhibitory activity against human bone marrow cells.

Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study.

Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospectively randomized to receive either radiation alone or radiation and adjuvant estrogen (diethylstilbestrol). No patient had received any prior definitive treatment for cancer. Forty patients were randomized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen.

Prostaglandin production by murine tumors as a predictor for therapeutic response to indomethacin.

We investigated whether there is a relationship between the production of eicosanoids by murine solid tumors and their response to the prostaglandin H (PGH) synthase inhibitor indomethacin. Three sarcomas, designated FSA, NFSA, and SA-NH, and two carcinomas, designated MCA-K and HCA-I, syngeneic to C3Hf/Kam mice were used. In general, FSA and NFSA produced more PGH synthase products than lipoxygenase products, whereas HCA-I produced both types of metabolites in large quantities.

Branhamella catarrhalis septicemia in patients with leukemia.

During a 10-year period, four patients with leukemia were identified who had Branhamella catarrhalis septicemia. Two patients had acute leukemia and the remaining two had chronic myelogenous leukemia with blastic transformation. All patients were febrile and neutropenic at the onset of the septicemia.

Ulex europeus type I agglutinin detects carcinoembryonic antigen in extracts of human colorectal carcinoma.

Recent interest has focused on fucosylated epitopes expressed on human neoplasms. The plant lectin Ulex europus agglutinin, Type I (UEA) binds fucosylated oligosaccharides, while UEA-reactive substances have a tissue distribution similar to carcinoembryonic antigen (CEA). We sought to determine if UEA reacted with CEA in extracts of fresh primary and metastatic colorectal carcinomas and paired normal tissues.

Signet-ring-cell carcinoma of the prostate. Electron-microscopic and immunohistochemical studies of eight cases.

Primary signet-ring-cell carcinoma of the prostate is extremely rare. We report eight patients with prostatic adenocarcinomas containing significant numbers of signet-ring cells, one of whom presented initially with supraclavicular lymph node metastasis. Patient ages ranged from 50 to 80 years (mean, 67.

Estrogen receptor and hormone responsiveness of medullary thyroid carcinoma cells in continuous culture.

We have examined the estrogen responsiveness and estrogen receptor in medullary thyroid carcinoma using a model of an established human cell line, TT. TT cells bind [3H]estradiol with high affinity. Scatchard analysis reveals a single class of binding site with a concentration of 173 fmol/10(6) cells and a dissociation constant of 2.

Establishment and characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck.

Two human cell lines were established from untreated squamous cell carcinomas of the head and neck. Line 183 was derived from a head and neck squamous cell carcinoma of the tonsil and 1483 from a head and neck squamous cell carcinoma of the retromolar trigone. Both lines grow in a cobblestone pattern demonstrating their epithelial heritage.

Characterization of mono-, di-, and tri-O-acetylated sialic acids on human cells.

The presence of mono-, di-, and tri-O-acetylated sialic acids on human cells was demonstrated by using radiochromatographic and chemical techniques. Human melanoma cells and fresh colon tissue were biosynthetically labeled with 6- (3H) glucosamine. Radiolabeled sialic acids were hydrolytically removed from cellular glycoconjugates, purified by ion-exchange chromatography, and separated by paper chromatography on the basis of the number of O-substitutions on each sialic molecule.

Analysis of cell surface glycoprotein changes related to hematopoietic differentiation.

A high-resolution technique has been used to study differentiation-related and leukemia-associated glycoproteins. Cells are labeled with the membrane-impermeable probe sulfo-N-hydroxysuccinimidyl-biotin. Nonionic detergent extracts are subjected to affinity chromatography on a number of immobilized lectins and after polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE) and western transfer, the biotin-labeled glycoproteins are visualized by using avidin-horseradish peroxidase and 4-chloronaphthol.

Differential expression of a sialoglycoprotein with an approximate molecular weight of 900,000 on metastatic human colon carcinoma cells growing in culture and in tumor tissues.

Wheat germ agglutinin (WGA)-binding cellular glycoproteins produced by HT-29 human colon carcinoma and its variant cells established from liver metastases in nude mice after intrasplenic injection were analyzed by polyacrylamide gel electrophoresis. On 5.5% polyacrylamide gels five major sialoglycoproteins (approximate Mr 115,000, 145,000, 190,000, 450,000, and 740,000) reactive with WGA were common to the parental and metastatic sublines.

Endogenous lectins as mediators of tumor cell adhesion.

Endogenous carbohydrate-binding proteins have been found in various normal tissues and cells. Although lectins with different sugar-binding specificities have been described, the most prevalent ones are those that bind beta-galactosides. The ability of some normal and malignant cells to bind exogenous carbohydrate-containing ligands suggested that lectinlike activity is associated with the cell surface and that carbohydrate-binding proteins might mediate intercellular recognition and adhesion.

Neutron therapy in cervical cancer: results of a phase III RTOG Study.

Between October 1976 and May 1984, 156 patients with locally advanced cervical cancer were entered into a Phase III trial with the participation of five institutions. Patients were randomly assigned to receive photons only (50 Gy in 25 fractions over 5 weeks plus intracavitary applications or external-beam boost) or mixed-beam radiotherapy (2 fractions a week of neutrons, 3 fractions a week of photons to a total RBE-adjusted dose of 50 Gy over 5 weeks plus intracavitary applications or external mixed-beam boost). Only patients with squamous carcinoma of FIGO Stages IIB, III, or IVA with negative para-aortic nodes on lymphangiogram were eligible.

Effect of recombinant granulocyte/macrophage colony-stimulating factor on human monocyte activity in vitro and following intravenous administration.

The purpose of these studies was to examine the antitumor properties of blood monocytes from patients undergoing a phase I trial with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF). Peripheral blood monocytes from 7 patients receiving various doses of rGM-CSF by continuous infusion were isolated prior to therapy and at various times during the 2-wk infusion. Monocytes/cubic centimeter of blood increased in a dose-dependent fashion in patients receiving rGM-CSF.

Protein-carbohydrate complementarity in mammalian gamete recognition.

Recent studies suggest that gamete recognition in a number of species is mediated by complementary proteins and carbohydrates on opposing gamete surfaces. Studies in invertebrates and vertebrates have shown that carbohydrate-binding proteins on the sperm surface recognize and bind to complementary glycoconjugates on the egg's extracellular coat. This chapter reviews our current knowledge of gamete recognition in the mouse.

The significance of müllerian inclusions found at second-look laparotomy in patients with epithelial ovarian neoplasms.

When no visible tumor is identified at second-look laparotomy, selected biopsy specimens or cytologic washings may reveal microscopic tumor or benign pathologic atypia. The pathology material from 311 patients with epithelial ovarian carcinoma who had no macroscopic tumor at second-look laparotomy was evaluated for psammoma bodies, müllerian inclusions (benign glandular inclusions), microscopic tumor, and either inflammation or fibrosis. Progression-free intervals and survival rates were influenced by the presence of müllerian inclusions (favorably), tumor or positive cytology (unfavorably), and inflammation or fibrosis (unfavorably).

Chordoma. An immunohistochemical study of 20 cases.

Twenty chordomas from 20 patients, including 17 nonchondroid and three chondroid types, were studied with a variety of antibodies directed against cytokeratin (AE-1/3), epithelial membrane antigen, carcinoembryonic antigen, S100 protein, vimentin, alpha 1-antichymotrypsin, and lysozyme. All 17 nonchondroid chordomas stained for cytokeratin, and most (16) stained for epithelial membrane antigen. In contrast, two chondroid chordomas failed to stain for either cytokeratin or epithelial membrane antigen, while one of them did stain for both antigens.

UV-induced photoproducts of 5-methylcytosine in a DNA sequence context.

In order to detect possible m5C photoproducts, highly purified rat liver DNA-cytosine methyltransferase was used to specifically generate m5C with a radioactive methyl group. When these DNAs were subjected to a large dose (10 kJ/m2) of 254 nm or 302 nm ultraviolet light (UVB) to enhance the yield, two labeled photoproducts were detected and isolated by reverse phase HPLC after formic acid hydrolysis. Further studies using acetone as a triplet state sensitizer and UVB irradiation suggested that photoproduct II was activated via a triplet state while the more polar photoproduct I was not.

Effect of radiation-induced injury of tumor bed stroma on metastatic spread of murine sarcomas and carcinomas.

The study was performed to determine whether irradiation of the tumor bed alters the propensity of tumors to metastasize, and if so, whether the effect is dependent on the property of tumors to exhibit the tumor bed effect (TBE). Ten tumors, of which 5 were sarcomas and 5 were carcinomas syngeneic to C3Hf/Kam mice, were used. Tumors were grown s.

Stage II endometrial carcinoma. Results and complications of a combined radiotherapeutic-surgical approach.

Since one third of the patients with Stage II endometrial carcinoma have occult extrauterine pelvic metastases at diagnosis, adequate treatment must include the pelvic lymph nodes and parametria. Eighty-three patients with Stage II endometrial carcinoma were treated between January 1964 and December 1983. Sixty-nine patients (83%) received combined whole-pelvic irradiation and surgery, five (6%) had surgery alone and nine (11%) had radiotherapy alone.

Influence of organ microenvironment on pigmentation of a metastatic murine melanoma.

The purpose of these studies was to investigate the relationship of the host microenvironment to the metastatic and pigmented phenotypes of the SW-1 variant of the murine K-1735 melanoma. The SW-1 subline was isolated from an amelanotic lung metastasis in a C3H/HeN mouse given an s.c.

Phase II study of AMSA alone and in combination with DTIC in patients with metastatic melanoma.

A randomized phase II study of AMSA (amsacrine) alone and AMSA combined with DTIC (dacarbazine) was carried out in 31 and 39 patients with metastatic melanoma respectively. AMSA was used at a starting dose of 40 mg/m2/day X 3 days with escalation to 50-60 mg/m2/day X 3 days in 8 pts. For AMSA + DTIC the starting dose was: AMSA 30 mg/m2/day X 3 days; DTIC, 800 mg/m2 X 1 day.