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P Calabresi

Publications and source records attributed to P Calabresi.

At least 253 records · Page 14Linked to original sources
PubMed1982

Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro.

The responses of two heterogeneous human cancer cell lines and their derivative clones to graded single doses of X-rays were examined in vitro. One system consisted of the human colon carcinoma line DLD-1 and two subpopulations (clones A and D). The second system consisted of the human lung carcinoma line (LX1) and four subpopulations (LX1-1, LX1-2, LX1-3, and LX1-9). These subpopulations have previously been shown to be markedly heterogeneous in terms of such characteristics as karyotype, morphology, drug sensitivity, tumorigenicity, and expression of membrane glycoproteins (such as carcinoembryonic antigen and tumor colonic mucoprotein antigen). Exponentially growing cultures were irradiated with graded single doses of 100-kVp X-rays. Survival was assessed using colony formation as the end point, and responses from multiple experiments were fitted to the single-hit, multitarget equation of cell survival. Values for the mean lethal dose (D0, grays), quasithreshold dose (Dq, grays), and extrapolation number (n) were obtained. For the human colon adenocarcinoma system, these values for the three tumor lines were: DLD-1, 0.95, 2.34, and 11.7; clone A, 1.06, 2.23 and 8.20; and clone D, 1.08, 1.89, and 5.80. For the human lung carcinoma system, these values for the five sublines were: LX1, 1.14, 0.19, and 1.20; LX1-1, 0.96, 2.06, and 8.54; LX1-2, 0.98, 0.88, and 2.48; LX1-3, 0.68, 2.05, and 20.3; and LX1-9, 1.12, 0.00, and 1.00. These two human tumor systems therefore exhibit variability in their intrinsic sensitivity to X-irradiation. The data indicate that failure of some human carcinomas to respond to physical treatment modalities can be due to preexisting resistant subpopulations.

Adenocarcinoma↗
PubMed1982

Establishment and characterization of two human pancreatic cancer cell lines tumorigenic in athymic mice.

Two human pancreatic cancer lines, RWP-1 and RWP-2, have been established from 2 patients with primary pancreatic cancer metastatic to the liver. The patients' tumors, the xenografted tumors, and tumors obtained by inoculation of nude mice with cultured RWP-1 and RWP-2 cells are all moderately-well-differentiated ductal cell adenocarcinomas. Ultrastructural analysis supports the tissue histopathology findings. Xenografts of RWP-1 tumors double every 10 days, whereas the doubling time of RWP-2 xenografts is 22 days. Both tumors contain mucin. RWP-1 and RWP-2 cells have a doubling time in culture of 45 hr and form colonies in soft agar. RWP-1 cultures appear to be morphologically heterogeneous; two distinct epithelial cell types can be identified. RWP-1 and RWP-2 have modal chromosome numbers of 64 and 62, respectively. Appreciable levels of glucose-6-phosphate dehydrogenase and lactic dehydrogenase were found in both cell lines and xenografts. RWP-1 and RWP-2 cells produce appreciable amounts of carcinoembryonic antigen, 1090 and 414 ng/10(6) cells, respectively.

Adenocarcinoma↗
PubMed1982

Inhibition of the growth of human colon cancer xenografts by polar solvents.

The effects of N,N-dimethylformamide (DMF) and N-methyl-formamide (NMF) on the growth of two human colon cancer cell lines xenografted in nude mice were assessed. Toxicological studies with mice heterozygous for the nu/nu gene showed that with both compounds the limiting organ toxicity was hepatic. The 10% lethal doses for DMF and NMF given i.p. daily for 21 days were 2219 and 374 mg/kg, respectively. Nude mice (10/group) received s.c. transplants of HCT-15 or DLD- 2 human colon cancer cells. Mice were treated i.p. with the approximate 10% lethal doses of either DMF (daily for 21 days) or NMF (daily for 19 days) or with 0.9% NaCl solution when tumors became palpable. With the HCT-15 tumor, a growth inhibition of 65% was obtained using DMF compared to 0.9% NaCl solution-treated controls. Two independent experiments with DLD-2 demonstrated that DMF effected growth inhibitions of 45 and 67%. NMF treatment produced 48 and 75% growth inhibitions of HCT-15 and DLD-2 tumors, respectively. Weight loss of groups of treated mice in all experiments was between 2 and 14%, within the acceptable range for 10% lethal drug doses. Results indicate that some human cancer xenografts respond to the polar solvent DMF and to its metabolite NMF and that DMF may be acting at least in part by its metabolism to NMF. Furthermore, the data should alert clinical investigators to the possibility of hepatotoxicity when polar solvents are tested in Phase I clinical trials.

Animals↗
PubMed1981

Heterogeneity of cancer cells from a single human colon carcinoma.

The human colon carcinoma cell line DLD-1, established from tumor tissue obtained from a 45 year old white man with an adenocarcinoma of the sigmoid colon, was studied from the perspective of tumor heterogeneity. The karyotype and morphology of cells from an early passage DLD-1 culture, as well as the histologic features of both the original tumor and neoplasms produced by inoculation of athymic nude mice with DLD-1 cells, indicated that both the DLD-1 cell line and the original tumor were heterogeneous. Two clones were isolated from the DLD-1 line; they differed in their morphology, karyotype, and cloning efficiency in soft agar. Furthermore, when cells from each clone were injected into athymic mice, histologically distinct tumors were produced. Various analyses showed that the two cloned lines were representative of the two subpopulations predominantly responsible for the heterogeneity of the original neoplasm. In vitro drug screening results demonstrated that the two cloned lines have differential sensitivities to chemotherapeutic agents. The parent DLD-1 human colon carcinoma cell line and its two cloned subpopulations provide material for the study of various aspects and implications of human cancer cell heterogeneity.

Adenocarcinoma↗
PubMed1980

Cytotoxic liponucleotide analogs. II. Antitumor activity of CDP-diacylglycerol analogs containing the cytosine arabinoside moiety.

Among events limiting the effectiveness of cancer chemotherapy are the general lack of preferential uptake of anticancer drugs by tumor cells and the occurrence of drug resistance. An approach has been undertaken to explore whether or not such events can be favorably altered or circumvented therapeutically by development of a new class of anticancer molecules, cytotoxic liponucleotide analogs. The design of cytotoxic liponucleotide analogs encompasses both biochemical and biophysical aspects of liponucleotide and glycerophospholipid structure and metabolism. Several cytotoxic liponucleotide analogs of cytidine diphosphate diacylglycerol (CDPdiacylglycerol/dCDPdiacylglycerol), containing the 1-beta-D-arabinofuranosyl moiety, were tested for antitumor activity. Multispecies ara-CDPdiacylglycerol (1-beta-D-arabinofuranosylcytosine 5'-diphosphate diacylglycerol), which contains egg lecithin-derived mixed fatty acyl chains, was more active than 1-beta-D-arabinofuranosylcytosine (ara-C), a clinically used anticancer drug, against leukemia L5178Y and P388 ascites cells in mice. At identical single doses (50 mg/kg per day times 4) administered intraperitoneally, ara-CDPdiacylglycerol prolonged the life spans of L5178Y tumor-bearing mice 93%, while ara-C prolonged life by 18%. Ara-CDPdiacylglycerol increased life spans of P388 tumor-bearing mice by 357% at doses of 50 mg/kg per day times 4; the maximum increase with ara-C was 159% (85 mg/kg per day times 4). Against a P388 ara-C-resistant cell line (P/Ara-C, kinase deficient) in mice, ara-CDPdiacylglycerol prolonged survival times by 34% at a dose of 50 mg/kg per day times 4 and by 55% at 75 mg/kg per day times 4; the drug was not active against two other ara-C-resistant murine leukemia mutants (CA 55, CA5b). With cell line-derived human colon carcinoma HCT-15 grown in mice immunosuppressed with anti-thymocyte serum, ara-CDPdiacylglycerol at a single daily dose of 50 mg/kg per day times 4 significantly reduced tumor weights to 21% of the controls; the same dose schedule of ara-C caused no observable reduction of tumor weights. Results of these preliminary antitumor evaluations indicate that cytotoxic liponucleotide analogs should be investigated further to determine their potential as antineoplastic molecules.

Animals↗
PubMed1979

Successful therapy of crystalcryoglobulinemia: a case report.

Successful therapy for a case of multiple myeloma with a spontaneously crystallizing cryoglobulin of the IgG2-kappa light chain variety was achieved, using both continuous-flow cell centrifugation plasmapheresis to rapidly lower the M component and combination chemotherapy with phenylalanine mustard, prednisone, procarbazine, and vincristine to control the myeloma process. This resulted in resolution of incapacitating large and small necrotic cutaneous ulcerations of the extremities. Physicochemical studies of the crystalcryoprotein demonstrated that cryoprecipitation was rapid and accompanied by the formation of needle-shaped crystals, yet was completely reversible at 37 degrees C. Cryocrit determinations varied depending upon relative centrifugal forces and temperature and did not always relate linearly to the amount of abnormal protein, thus making these alone unreliable in assessing response to therapy.

Antineoplastic Agents↗
PubMed1979

Clinical trial of weekly pyrazofurin.

Pyrazofurin was administered to 21 patients with solid tumors at a dose of 200 mg/m2 iv weekly, because this dose had been shown to be well-tolerated and pharmacologic effects of a single dose at this level persisted for up to 7 days. An anemia consistent with a disturbance in rbc production was seen in most patients. Other toxic effects included stomatitis, rash, and myelosuppression. No complete or partial responses were noted, but two patients with alveolar cell carcinoma of the lung each had stable disease for 12 months. Most of the patients in this study tolerated the weekly dosage schedule well with only minimal myelosuppression, suggesting that this agent and schedule might be acceptable for use in combination chemotherapy. Several theoretic reasons favor the use of pyrazofurin in this manner. Pyrazofurin should also be evaluated more fully in patients with polycythemia vera, mycosis fungoides, and psoriasis, since other orotidylate decarboxylase inhibitors have been shown to be effective in these diseases.

Adult↗
PubMed1979

Phase I study of 5-fluorodeoxyuridine plus cytosine arabinoside infusions in patients with solid tumors.

A phase I trial was conducted in 30 patients with solid tumors, using infusions of 5-fluorodeoxyuridine (5-FUdR) plus cytosine arabinoside (ara-C). Doses of 5-FUdR administered over 2 hours daily X 5 ranged from 0.02 to 1.0 mg/kg, and these doses immediately preceded a 1-hour infusion of ara-C. These schedules were selected because 5-FUdR pretreatment had been shown to sensitize L5178Y cells in culture to acute cell death by ara-C. Dose-limiting toxicity was myelosuppression. Based upon results in this study, the recommended dose of 5-FUdR to be used in phase II trials of this combination is 0.04--0.05 mg/kg (1.6--2.0 mg/m2) given prior to ara-C at a dose of 100 mg/m2. Antitumor responses were seen in patients with head and neck cancer, breast carcinoma, and carcinoid syndrome.

Adolescent↗