Tumor necrosis factor and human hematopoiesis: II. Inhibition and mode of action on normal and chronic myelogenous leukemia-derived granulocyte-macrophage progenitor cells.

Recombinant technology-produced tumor necrosis factor alpha (rTNF-alpha) inhibits clonogenic growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) when it is continuously present in the culture medium. In our studies, day 7 and day 14 GM-CFC were inhibited and showed similar response. A decrease in the number of large colonies accounted for most of the inhibition, whereas growth of small clusters was inhibited to a lesser extent.

Aberrant expression of the K-ras proto-oncogene in B-cell malignancies.

The proto-oncogenes have the capacity for conversion to an oncogene that is capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in the neoplastic transformation of B-cell malignancies, we have analyzed their expression in 18 fresh samples obtained from the peripheral blood of patients with a variety of B-cell malignancies. A high-molecular weight c-k-ras transcript (5.

Polyethylene glycol-L-asparaginase and L-asparaginase studies in rabbits.

Injections of polyethylene glycol (PEG)-L-asparaginase or L-asparaginase were given to two rabbits each at doses of 40 units/kg. Ten min following injection of either enzyme preparation, the plasma enzyme concentration was approximately 1 unit/ml. This level decreased steadily in the rabbits given L-asparaginase, with a t1/2 of approximately 20 hr.

The effects of tin-protoporphyrin administration on hepatic xenobiotic metabolizing enzymes in the juvenile rat.

The heme analogue tin-protoporphyrin IX (SnP) is a potent inhibitor of microsomal heme oxygenase. Administration of SnP to neonatal rats can prevent hyperbilirubinemia by blocking the postnatal increase of heme oxygenase activity. Apparently innocuous at therapeutic doses, it is of potential clinical value for chemoprevention of neonatal jaundice.

Fine-needle aspiration cytology of pediatric patients with primary hepatic tumors: a comparative study of two hepatoblastomas and a liver-cell carcinoma.

The cytologic features of fine-needle aspirates (FNA) of two hepatoblastomas (HBs) and a liver-cell carcinoma (LCC) occurring in three children, ages 1, 3, and 14 yr, are presented. Electron microscopic features of one of the HBs and the LCC are also included. The HBs displayed single or small aggregates or larger clusters of cells with a high nuclear-cytoplasmic ratio and usually round, hyperchromatic nuclei with single, and occasionally double, prominent nucleoli.

Does interleukin 2 stimulus-response coupling result in generation of intracellular second messengers?

The binding of interleukin 2 (IL 2) to specific cell surface receptors provides a unique proliferative stimulus to sensitive T-lymphocytes. The purpose of this investigation was to examine the hypothesis that IL 2 stimulus-response coupling in the IL 2-dependent murine T-lymphocyte clone CTLL-2 employed some of the intracellular second messengers used by other growth factors. No evidence was obtained to implicate changes in intracellular Ca2+ concentrations, protein kinase C activation, or stimulation of the Na+/H+ antiporter or the Na+/K+ ATPase as requirements for stimulation by recombinant human IL 2.

Integration of cellular-SV40 DNA and the thermal stability of the recombinant sites. Brief report.

We calculated the predicted melting profiles of evolutionary variants of SV40 and compared the nucleotide sequences of large T antigen binding sites and recombinant sites for homology. Neither is critically important in selecting a recombinant site for SV40-SV40 and SV40-cellular DNA fragments.

Prevalence of human papillomavirus in inverted nasal papillomas.

Human papillomaviruses (HPVs) have been associated with both benign and malignant neoplasms of the head and neck. To determine the prevalence and types of HPVs in this neoplasm, we examined fixed tissue from 21 patients by in situ hybridization. Human papillomavirus types 6b and 11 probes were used, and hybridization was positive to both types in lesions from 16 (76%) of 21 patients.

Pleomorphic adenoma of parotid with myoepithelial cell predominance.

Primary tumors of the parapharyngeal space are uncommon. We herein report a case of a pleomorphic adenoma of the parotid gland in a 43-year-old woman who presented with a parapharyngeal mass that was initially interpreted as a soft tissue sarcoma. Electron microscopic and immunohistochemical studies demonstrated the myoepithelial origin of the tumor.

Cartilage sulfation inhibitor from rat liver: partial characterization of properties and biologic action.

Cartilage sulfation (somatomedin) inhibitors (CSI) from rat liver produce reversible inhibition of cartilage growth. After gel filtration Sephadex G-200, CSI appear to have MW approximately 100,000 and they are urea- and trypsin-labile factors. To explore further the mechanism of CSI action, we used the chick pelvic rudiment bioassay and studied the effect of CSI on the incorporation on 35S-sulfate (proteoglycan synthesis), 14C-leucine (protein synthesis), 3H-uridine (RNA synthesis), and 3H-thymidine (DNA synthesis).

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia.

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4-hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay.

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte--macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period.

A comparison of the effects of cisplatin and N-methyliminodiacetato-(1,2-diaminocyclohexane)-platinum(II) on renal function and gentamicin excretion in rats.

N-methyliminodiacetato(1,2-diaminocyclohexane)-platinum(II) (MIDP) is a new third-generation water-soluble antitumor platinum complex. This study compares the effects of MIDP (3 injections of 25 mg/kg each on days 1, 5 and 9) on renal structure and function and the urinary excretion of gentamicin (GENT) with those of a single 6 mg/kg dose of cisplatin (DDP) in F-344 (Fischer) rats. GENT was given as a single dose of 30 mg/kg 7 days after DDP injection or the last MIDP injection.

Seminal vesicle involvement by in situ and invasive transitional cell carcinoma of the bladder.

We report six cases of seminal vesicle involvement by transitional cell carcinoma of the bladder among 187 consecutive cystoprostatectomy specimens. Two of these six cases showed mucosal spread without stromal invasion (type A); the remaining four cases presented a direct extension (type B) from muscle-invasive carcinomas of the bladder. Type A involvement of the seminal vesicle was associated with a long history of superficial bladder cancer with similar mucosal spread to the prostatic ducts, acini, and ejaculatory ducts.

The significance of residual tumor after preoperative pelvic irradiation for stage II endometrial carcinoma.

The prognostic significance of residual endometrial carcinoma in the hysterectomy specimen after preoperative radiotherapy is controversial. Sixty-two patients with stage II endometrial carcinoma were treated with a standardized program of preoperative radiotherapy, followed in six weeks by an extrafascial hysterectomy. Twenty patients (32%) had no residual carcinoma in their hysterectomy specimens and 42 (68%) had residual carcinoma.

Melanoma arising in a spinal nerve root. Case report.

Melanotic neoplasms of the spinal nerve root are rare but well-documented occurrences. The authors report the case of a 68-year-old woman with a malignant melanotic neoplasm containing premelanosomes and melanosomes and lacking a basal lamina. This tumor was found in a lumbar nerve root and is believed to represent an instance of a primary melanoma arising in a spinal nerve root.

Comparison between clinical response and in vitro drug sensitivity of primary human tumors in the adhesive tumor cell culture system.

The newly described adhesive tumor cell culture system (ATCCS) offers a distinct advantage over other assays in that it has a high plating efficiency requiring low cell inoculum, it affords workable assays in approximately 70% of specimens from the heterogenous tumor types, and it has the ability to assay up to nine drugs at four different concentrations. Clinical correlations based on the ATCCS were obtained in 65 patients undergoing 71 clinical trials. Patients with melanoma, lung cancer, and sarcoma dominated the group.

The kinetics of repair in mouse lung after fractionated irradiation.

The kinetics of repair of sublethal damage in mouse lung was studied after fractionated doses of 137Cs gamma-rays. A wide range of doses per fraction (1.7-12 Gy) was given with interfraction intervals ranging from 0.

Cancer in survivors of childhood soft tissue sarcoma and their relatives.

One hundred fifty-nine 3-year survivors of childhood soft tissue sarcoma and their relatives were surveyed to determine the frequency of second malignant neoplasms (SMNs) in patients and cancer in their relatives. The cancer experience of the patients, their offspring, siblings, parents, parental siblings, and grandparents was compared to that expected of the general population based on age-, sex- and calendar year-specific rates from the Connecticut Tumor Registry. A significant excess of SMNs was observed in the patients (observed expected = 8:0.