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Biomedical subjects

F Calvo

Publications and source records attributed to F Calvo.

At least 109 records · Page 6Linked to original sources
PubMed1990

Phase I study of oxaliplatin in patients with advanced cancer.

Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3-4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1-2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of parethesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6-13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.

Adult↗
PubMed1990

Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity.

Natural and lymphokine activated killer cells (NK and LAK) are believed to play an important role in the control of tumour progression and metastasis. Their specific receptors on tumours cells are still unknown. Several studies suggest that these cells recognise and eliminate abnormal cells with deleted or reduced expression of MHC class I molecules. Previous reports suggest that interferons (IFN), by increasing MHC class I expression on target cells, induce resistance to killing by NK cells. We investigated the role of MHC molecule expression by two human breast cancer cell lines T47D and ZR75-1 in their susceptibility to NK and LAK cells. These two cell lines spontaneously express low levels of HLA class I antigens but no HLA class II molecules. After IFN-gamma treatment they both overexpressed MHC class I and de novo expressed class II molecules as detected by flow cytometry, quantified by a radioimmunoassay and analysed by two-dimensional gel electrophoresis. Opposed to untreated cells these IFN-gamma treated cells were resistant to NK and LAK lysis. Furthermore, preincubation of IFN-gamma treated breast cancer cells with F(ab')2 fragments of monoclonal antibodies to HLA class I and HLA class II molecules was unable to restore lysis. In contrast, several complete monoclonal antibodies including anti-HLA class I and HLA class II induced the lysis of target cells whether or not they had been treated by IFN-gamma. The therapeutic use of monoclonal antibodies directed against antigens expressed on tumour cells (ADCC) in conjunction with interferon therapy should be discussed in lymphokine-based strategies for treatment of cancer patients.

Adenocarcinoma↗
PubMed1989

Characterization and distribution in normal and tumoral human tissues of breast cancer-associated antigen defined by monoclonal antibody 7B10.

Monoclonal antibody 7B10, raised against the human breast cancer cell line T47D, identifies an antigen found in human breast carcinomas and in normal breast. Western blot and immunoprecipitation studies detected a Mr 76,000 antigen in cytosol, cell membrane, and cell culture supernatants of T47D cells. 7B10 binding to T47D cell extracts was affected by proteolytic digestion with protease type VI, trypsin, and subtilisin while it was not altered by neuraminidase digestion. Adsorption of breast cancer cell line extracts with concanavalin A reduced 7B10 immunoreactivity more than 70%. These results suggest that the antigen is a glycoprotein and that the epitope does not contain sialic acid. 7B10 was reactive with neither human milk fat globule membrane, nor skimmed milk, nor the milk-derived HBL 100 cell line. Conversely binding was detected in more than 50% of normal breast epithelial cells in culture. 7B10 immunostaining was positive on frozen sections of normal breast and nonmalignant mastopathies in 30 to 90% cells. In frozen sections of other normal tissues, 7B10 immunoreactivity was detected only in colon, apocrine glands of skin, parotid ducts, and luteal phase endometrium, confirming previous data on paraffin sections. Strong, homogeneous immunostaining was observed on frozen sections of intraductal and invasive lobular breast carcinomas (100% of cases), while more heterogeneous staining was found on invasive ductal carcinomas. Colon and rectal carcinomas, one carcinoma of the esophagus, and some cells in serous ovarian carcinomas also showed 7B10 reactivity. Immunoblotting of the 7B10-immunoreactive fraction isolated by Sepharose CL-6B chromatography of a breast carcinoma tissue sample extract identified the Mr 76,000 antigen, which was also detected in several breast cancer specimens, in colon adenocarcinomas, and in serous ovarian carcinoma fresh tumor extracts. The Mr 76,000 glycoprotein described here represents a breast cancer-associated antigen previously undescribed, mainly expressed in normal breast and breast tumors.

Antibodies, Monoclonal↗
PubMed1989

[Solitary splenic abscess. Clinical picture, diagnosis and treatment].

Splenic abscess, especially the solitary type, is a rarely seen condition, although it has been seen more frequently in recent years. On the basis of a case of splenic abscess with unusual features, the literature on the subject, 171 cases published in Italy, Britain, France and Spain in the past 10 years, is reviewed. It is pointed out that the diagnosis is generally difficult only because abscess is not considered. The diagnostic methods with the best results are ultrasonography and CT scanning, although a checkup after the event showed that straightforward X-ray of the chest, if correctly interpreted, may be enough. Scintigraphy is not indicated and arteriography should only be used in the event of special problems. The clinical picture is scanty and insignificant. The various aetiological agents and changes in these over recent years are illustrated, with special attention with regard to immunodepressed patients. The usual treatment is surgical removal. Other methods with more limited indications, such as drainage and medical treatment, are described.

Abscess↗
PubMed1989

[Culturing of normal and tumor cells of the human prostate].

Cell lines of neoplastic human prostate gland tissue are uncommon. We studied the condition of long term prostatic cell culture; 18 primary cultures of epithelial prostatic cells and 15 subcultures were maintained for several months. The optimum medium for primary prostatic cell cultures contains: little calcium, epithelial growth factor (EGF), phosphoethanolamine, spermine and cholera toxin, the cell characterisation for cultivation of normal, hyperplastic and neoplastic prostate gland tissue in subcultures uses monoclonal antibody against cytokeratin, prostatic acid phosphatase and prostatic specific antigen.

Adenocarcinoma↗
PubMed1989

[Role of monoclonal antibodies in the study of breast cancer].

Breast cancer is the most frequent cancer among women in western countries, where it represents about one third of tumors. Many laboratories utilized monoclonal antibodies technology for studying this pathology and for clinical applications. Different immunisation strategies have been utilized in the aim to produce monoclonal antibodies specific of mammary epithelial cells, of cancer cells or of cell secretions products. Despite efforts none of these are entirely specific, either for the normal tissue or for malignant tumors derived from it. However several of them had applications in fundamental study of oncogenesis and/or in tumor diagnostic, and in therapeutic assays. In this review we analysed described monoclonal antibodies, their reactive antigens and their applications.

Antibodies, Monoclonal↗
PubMed1988

Pharmacology, molecular identification and functional characteristics of vasoactive intestinal peptide receptors in human breast cancer cells.

High-performance liquid chromatography-purified 125I-vasoactive intestinal peptide (VIP) bound to T-47D human breast cancer cells in a specific, saturable, and reversible manner. Scatchard plots were compatible with the presence of one class of VIP receptors with high affinity (Kd = 4.5 X 10(-10) M VIP, and Bmax = 293 fmol/mg protein). The neuropeptide and its natural analogues inhibited the binding of 125I-VIP and stimulated cyclic AMP (cAMP) generation in T-47D cells 96-fold (EC50 = 7 X 10(-10) M VIP), in the following order of potency: VIP greater than helodermin greater than human peptide with N-terminal histidine and C-terminal methionine greater than human pancreatic growth hormone-releasing factor greater than human secretin. In contrast, 125I-VIP binding was not displaced by pancreatic glucagon, human oxyntomodulin, truncated glucagon-like peptide-1, glucagon-like peptide-2, the somatostatin analogue SMS 201-995, gastric inhibitory peptide, and a series of steroid hormones or peptides unrelated to VIP. VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1. Adenylate cyclase activity rose from 72.2 +/- 14 to 1069 +/- 66 pmol cAMP/min mg protein after the addition of 10(-7) M VIP to T-47D plasma membranes. In agreement with our pharmacological results and the Scatchard analysis of the binding data, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor in the T-47D membranes permitted identification of one autoradiographic band with a molecular weight of 69,000. The sensitivity of the Mr 69,000 binding site to GTP and low doses of VIP implies that in T-47D cells, this component constitutes the membrane domain involved in the functional regulation of adenylate cyclase by VIP receptors. Our results indicate a role for the VIP receptor-cAMP system in human breast cancer cells.

Adenylyl Cyclases↗
PubMed1988

Intra-operative radiation therapy in the treatment of pelvic malignancies: a preliminary report.

Local control of advanced pelvic malignancies, particularly when complete surgical resection is not feasible, is often impeded by dosage limitations in radiation therapy and the intolerance to radiation of normal tissues. This is a preliminary report on the feasibility of improved local control in pelvic malignancies treated by intra-operative radiation therapy, as a radiation boost, in addition to conventional surgical resection and external beam radiation therapy. Fifteen gynaecological malignancies (five cervix, five uterus, four ovary, and one vulva) from Rush Medical College and the University of Navarre, as well as 36 other pelvic malignancies (32 colorectal, 4 genito-urinary) from Rush Medical College were reviewed. All tumours were advanced or recurrent, and all patients were felt to be at high risk of local failure. IORT was administered at a dose range of 10-26 Gy. Our data suggest that the probability of local control improves when IORT is used for primary and for microscopic disease, when the tumour is at least partially resectable, and when the total dose given in IORT and external beam radiation exceeds 70 Gy.

Brachytherapy↗
PubMed1988

Use of liquid culture and cell cycle analysis to compare drug damage following in vitro treatment of normal human bone marrow cells with adriamycin, arabinosyl-cytosine, and etoposide.

The effects of adriamycin (ADM), arabinosyl-cytosine (ARA-C), and etoposide (VP16) were studied on human bone marrow mononucleated cells using colony formation in agar, a modified liquid culture system, and flow cytometry analysis of the cell cycle. Drug concentrations tested during a 1-h incubation ranged from 0.1 to 4 micrograms/ml for ADM, from 0.3 to 30 micrograms/ml for VP16, and from 10(-7) to 10(-3) M for ARA-C. Regression analysis of the dose-response curves was used to assess the drug concentration that inhibited 90% +/- 5% (LD90) of colony growth. LD90s were 0.4 microgram/ml for ADM, 20 micrograms/ml for VP16, and 10(-4) M for ARA-C. LD90-surviving cells were cultured in liquid medium for 3 weeks. Surviving cells over this time were 13% of the control for ADM, 22% for VP16, and 95.7% for ARA-C. Although cells decreased drastically in ADM- and VP16-treated samples, granulocyte-macrophage colony-forming units (CFU-GM) per 10(5) surviving cells rose to twice the control for ADM, to 60% for VP16, and to 150% for ARA-C. Flow cytometry analysis of the cell cycle was performed at day 0 and at day 4 after treatment with the LD90 dose. It showed a rapid and reversible effect of ARA-C on cells in the S-phase, whereas the action of VP16 concerned all cells, regardless of their cycle phase. We conclude that the direct effects of the three drugs on CFU-GM in agar are poorly predictive of hematopoietic reconstitution capacity, except for VP16. Liquid culture gives a much more accurate appraisal of the long-term damage and recovery due to anticancer drugs.

Bone Marrow Cells↗
PubMed1988

[Organoplatinum compounds. 1987 update].

Cisplatin is one of the best available cytotoxic agents particularly in testicular, ovarian and head and neck cancer. However gastrointestinal and renal toxicities preclude greater utilisation. High dose cisplatin (200 mg/m2) has serious neurological side effects. Carboplatin gives the same therapeutic results as cisplatin in ovarian, small cell lung and head and neck cancers with a better tolerance, the main toxicity being haematological. Iproplatin seems to have no advantage over carboplatin. New derivates such as diaminocyclo-hexane-platinum seem to be promising in preclinical and phase I studies.

Carboplatin↗
PubMed1987

A novel monoclonal antibody (7B10) with differential reactivity between human mammary carcinoma and normal breast.

A monoclonal antibody (7B10) which displays differential reactivity with breast carcinomas compared to benign lesions or normal breast tissue was selected by fusion of spleen cells from BALB/c mice immunized with the T47D human mammary carcinoma cell line. The antigen, recognized by 7B10 on T47D cells, appeared to be both surface and cytoplasm localized, as demonstrated by indirect immunofluorescence, immunoperoxidase, and electron microscopy studies. This antibody (IgG1) bound with four human breast cancer cell lines (T47D, MCF7, ZR-75-1, and HSL53) which express estrogen receptors. No binding was observed with cancer cell lines of other origin or with normal cells. In vivo, by immunoperoxidase staining of frozen sections of normal breast, the antigen recognized by 7B10 appeared to be located on epithelial cell membranes, whereas in benign and malignant mammary disorders, staining also involved the cytoplasm, as confirmed by electron microscopy on fresh cancer tissue. On formalin-fixed, paraffin-embedded sections, cytoplasmic staining was detected in breast cancer, but no immunostaining was observed with benign lesions or normal breast. In paraffin sections, most normal tissues investigated did not react with 7B10 antibody. However, ducts in the parotid gland, tubules in the kidney and some biliary ducts, and apocrine glands in the skin showed irregular, diffuse weak staining. 7B10 was unreactive with adenocarcinomas of origin other than breast, except for some cells in ovarian clear cell carcinoma. No reactivity was observed with squamous carcinomas, lymphomas, or melanomas. The antigen recognized by 7B10 appeared to be a Mr 32,000 protein, as identified by immunoprecipitation from extracts of T47D after labeling with [35S]methionine. Since the antigen was present only on the membrane of differentiated normal mammary epithelial cells, and was also expressed in the cytoplasm of tumor cells, it may be of interest in immunological studies of mammary epithelial cell differentiation. Moreover, since in formalin-fixed tissues immunostaining is virtually confined to mammary carcinomas, monoclonal antibody 7B10 may have diagnostic applications in breast cancer.

Animals↗