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Biomedical subjects

A Lanza

Publications and source records attributed to A Lanza.

At least 37 records · Page 2Linked to original sources

Efficacy of epirubicin/paclitaxel combination in mobilizing large amounts of hematopoietic progenitor cells in patients with metastatic breast cancer showing optimal response to the same chemotherapy regimen.

BACKGROUND AND OBJECTIVE: Based on our preliminary experience, we have further evaluated the capacity of the paclitaxel/epirubicin combination (at the dose of 175 and 90 mg/m(2), respectively) plus G-CSF to mobilize hematopoietic progenitors into the circulation. DESIGN AND METHODS: The study was conducted in a homogeneous cohort of 25 stage IV breast cancer patients showing response to three cycles of the same chemotherapy regimen and who were included in a high-dose chemotherapy program. RESULTS: In most cases (68%) more than 5_10(6) CD34+ cells/kg b.w. (the threshold fixed in our study) were collected by a single leukapheresis, 28% and 4% of patients requiring 2 and 3 procedures, respectively. Based on the CD34+ cell count in the peripheral blood, most of the leukaphereses (53%) were performed on day 11 after chemotherapy. More than 50 CD34+ cells/mL along with a preleukapheresis WBC count between 10 and 20_10(9)/L predicted that only a single harvest would be required in 100% of cases. The evaluation of the clonogenic potential of collected cells showed that a large number of committed colony-forming cells (CFCs) and more primitive long-term culture-initiating cell (LTC-IC) hematopoietic progenitors were present in 20 harvests studied. INTERPRETATION AND CONCLUSIONS: These data demonstrate that the epirubicin/paclitaxel combination followed by G-CSF, besides being a very active regimen in MBC, is effective in releasing large amounts of progenitor cells into the circulation which can then be safely employed to support myeloablative regimens.

Adult↗

[Changes in the mouth mucosa in patients with chronic inflammatory intestinal diseases].

BACKGROUND: Oral mucosa and periodontal lesions occurrence in Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC) and Crohn Disease (CD). METHODS: This study involved 100 patients examined for 5 years (1990/1995), with a clinical and histopathological diagnosis of CD (21 patients) and UC (79 patients). RESULTS: The analysis of the data obtained, from our sample, showed that 5 patients out of 100 presented aphtha minor lesions; in 3 cases the diagnosis was, respectively, of two neoformations of the genian mucosa--which turned out to be a papilloma and a fibroma--and a retro-commissural leukoplakia, degree OIN I. The 50% of our patients presented parodontal lesions, oral candidosis in 15 out of 67 patients who presented a whitish coating on the back of the tongue. CONCLUSIONS: The results of this investigation, lessen the importance of an association between IBD and oral diseases.

Adolescent↗

[Basaloid squamous carcinoma of the tongue. Clinico-anatomical study of a case].

The basaloid squamous carcinoma was first described in 1986. It is a rare tumor with particular morphologic and biologic features that separate it from the more common squamous cell carcinoma of the head and neck region. A case with histologic diagnosis of basaloid squamous carcinoma of the tongue treated only with radiotherapy, is reported.

Aged↗

Hematopoietic progenitor cell collection and neoplastic cell contamination in breast cancer patients receiving chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization.

BACKGROUND: We compared hematopoietic progenitor cell (HPC) collection and neoplastic cell contamination in breast cancer patients given cyclophosphamide (CTX) plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization. PATIENTS AND METHODS: In 57 stage II-III breast cancer patients, CD34+ cells, colony-forming units-granulocyte macrophage (CFU-GM), early HPC and breast cancer cells were counted in HPC collections obtained after CTX plus G-CSF (n = 27) or G-CSF-alone mobilization (n = 30). RESULTS: The CD34+ cell collection was about two-fold greater after CTX plus G-CSF mobilization (11.0 +/- 7.9 vs. 5.8 +/- 3.5 x 10(6)/kg, P < 0.001). Similarly, the total number of CFU-GM, CD34+CD38- cells and of week-5 cobblestone area forming cells (CAFC) collected was significantly higher in patients mobilized with CTX plus G-CSF. Breast cancer cells were found in the apheresis products of 22% of patients mobilized with CTX plus G-CSF and in 10% of patients mobilized with G-CSF alone (P = 0.36). Of seven patients who failed G-CSF-alone mobilization and eventually underwent chemotherapy plus G-CSF mobilization, none had cytokeratin-positive cells after G-CSF mobilization, whereas four out of seven had cytokeratin-positive cells after chemotherapy plus G-CSF (P = 0.07 by chi 2 test). CONCLUSION: The CTX plus G-CSF mobilization protocol was associated with a significantly higher HPC collection. However, this benefit was not accompanied by a reduction in the incidence of tumor-contaminated HPC graft.

Adult↗

Epithelial tumour cell detection and the unsolved problems of nested RT-PCR: a new sensitive one step method without false positive results.

Sensitive detection of circulating epithelial cancer cells might have important therapeutic and prognostic implications in patients with breast cancer (BC) receiving high-dose chemotherapy and PBSC support. We have compared the specificity and sensitivity of the recently developed 'one tube' reverse transcriptase PCR (RT-PCR) assay with the more widely used nested RT-PCR method for detection of cytokeratin 19 (CK19)-positive cells. The analysis of 30 control samples provides evidence that one tube RT-PCR is highly specific in contrast to the nested method which showed 23% false positive results. The sensitivity of both techniques to detect tumour contamination was 10(-6). PBSC harvests from 45 BC patients were tested with both RT-PCR methods and the results were compared with immunocytochemistry (ICC). The five samples found positive by ICC were also positive by one tube RT-PCR; in addition, 11 more samples were positive by one tube RT-PCR analysis. The greater number of PBSC found positive by one tube RT-PCR might be due to the larger number of cells analysed. We conclude that one tube RT-PCR is sensitive and reveals no false positive results. This method is less time consuming than the nested one, technically simpler and should be considered for tumour cell detection.

Biomarkers, Tumor↗

Hematopoietic stem cells from different sources: biological and technical aspects.

Hematopoietic stem cell (HSC) enumeration is crucial to predict the engraftment potential of a given HSC collection, and currently involves the surrogate count of nucleated cells, CFU or CD34+ cells. However, there is raising evidence that CFU are HSC involved in short-term but not in long-term reconstitution, and that only a small fraction of all CD34+ cells have long term multilineage engraftment potential. In this regard, there is evidence that cord blood (CB), bone marrow (BM) and peripheral blood (PB) derived HSC are highly heterogeneous for a number of antigens useful for HSC enumeration by flow cytometry. Moreover, there is a raising evidence that a CD34 human HSC might exist. The CD34 HSC has been already described in animals and in human Hoechst 33342 negative HSC. This notwithstanding, clinical data have clearly demonstrated that purified allogeneic CD34+ cells can reconstitute the myeloid and the lymphoid lineages in myeloablated recipients. In the lack of a suitable marker for CD34 HSC enumeration, it is hard to predict the role of CD34 HSC in hematopoietic reconstitution after transplantation. On the other hand, these cells might be a better target for HSC expansion and gene transfer.

Antigens, CD34↗

Control of stem cell proliferation and differentiation to achieve stable gene transfer and expression.

Although the hematopoietic stem cell (HSC) seems to be a convenient target for gene therapy, data from human clinical trials have so far shown low levels of gene transduction. The new model of human stem cells, immunodeficient mice repopulating cells (SRC), has similarly demonstrated that SRC were rarely transduced by protocols used in past studies. Cytokines such as stem cell factor and interleukin-3, used so far to obtain cell proliferation in transduction protocols, might induce HSC to differentiate and impair their repopulating potential. In this scenario, there is a need for new gene transfer protocols associated with minimal cell differentiation and stable expression of the transduced gene in the majority of mature cells generated from transduced HSC.

Animals↗

Stem cell enumeration in cord blood vs bone marrow and peripheral blood.

Recent reports have suggested that the total number of autologous or allogeneic hematopoietic stem cell (HSC) infused after high-dose chemotherapy might predict survival, post-transplant morbidity and rate of hematopoietic engraftment. However, HSC capable of long-term multilineage potential are still poorly defined, and tools for accurate and reproducible HSC enumeration are highly warranted.

ADP-ribosyl Cyclase↗

Chromosomal fragility in the cancer-prone disease xeroderma pigmentosum preferentially involves bands relevant for cutaneous carcinogenesis.

Spontaneous and folate-induced chromosomal fragility was analyzed in peripheral blood lymphocytes from 6 patients affected by the cancer-prone disease xeroderma pigmentosum (XP), from the parents of 4 of the patients, and from 12 normal subjects. All XP patients were defective in nucleotide-excision repair; 4 belonged to group C and 1 each to groups A and D. A tendency toward increased spontaneous chromosomal fragility was observed in the XP family members, and lesions indicating substantial chromosomal damage, which were not observed in any healthy donors, were frequently found. The spontaneous lesion sites in lymphocytes from homozygous and heterozygous carriers of XP defects appeared to be significantly associated with those observed in normal skin fibroblasts from the same subjects. These XP spontaneous fragility sites showed a statistically significant association with the rearrangement breakpoints reported in skin pre-tumoral and tumoral lesions from normal and unrelated XP donors. Under conditions of folate deprivation, the chromosomal fragility level, the pattern and the frequency of expression of fragile sites in XP patients and in their parents were similar to normal. However, XP patients generally showed a higher susceptibility to breakage at sites described as mutagen and carcinogen targets.

Adolescent↗

Multilineage long-term engraftment potential of drug-resistant hematopoietic progenitors.

Peripheral blood progenitor cells (PBPCs) are increasingly used instead of bone marrow for autologous or allogeneic transplantation. In this study PBPCs mobilized in cancer patients by chemotherapy and granulocyte-colony stimulating factor were collected by apheresis and first enriched by immunoaffinity removal of lineage positive cells. When these cells were exposed to both cyclophosphamide and taxol or cultured for 7 days in the presence of 5-fluorouracil, stem cell factor, and interleukin-3, 88% to 93% of the enriched PBPCs were killed and short-term clonogenic capacity in methylcellulose assays was lost, but week-5 cobblestone area-forming cell (CAFC) enrichment was higher than 10-fold in comparison to enriched PBPCs and higher than 700-fold in comparison to unmanipulated apheresis cells. After drug exposure, most of the progenitors displayed a CD34+, CD38-, multidrug-resistance (MDR+), Rhodamine 123 low, Hoechst 33342 low phenotype, and as few as 180 of these drug-resistant cells were able to generate a stable multilineage human hematopoiesis in sublethally irradiated immunodeficient mice. In these animals, the level of human hematopoietic engraftment was significantly increased by cotransplantation of irradiated cells from the human L87/4 stromal cell line. These observations are consistent with the functional isolation of a population of very early hematopoietic progenitors and might help to design new protocols for the removal of neoplastic cells from autografts.

Animals↗

Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients.

We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1alpha. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection. MP proliferation peaked on day 7 in culture, and an 8- +/- 5-fold expansion of CD34+/CD61+ cells, a 17- +/- 5-fold expansion of colony-forming units-megakaryocytes, and a 58- +/- 14-fold expansion of the total number of CD61+ cells was obtained. In a feasibility clinical study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC) transplant received MP generated ex vivo (range, 1 to 21 x 10(5)/kg CD61 cells) together with unmanipulated PBPC. Eight patients received a single allogeneic platelet transfusion, whereas platelet transfusion support was not needed in 2 of the 4 patients receiving the highest doses of cultured MP. This result compares favorably with a retrospective control group of 14 patients, all requiring platelet transfusion support. Adverse reactions or bacterial contamination of cell cultures have not been observed. In conclusion, MP can be expanded ex vivo and safely administered to autologous transplant recipients. Further clinical trials will indicate the reinfusion schedule able to consistently abrogate the need for allogeneic platelet transfusion support in autologous transplantation.

Cells, Cultured↗

Role of tumor cells contaminating the graft in breast cancer recurrence after high-dose chemotherapy.

One of the possible drawbacks to autologous stem cell transplantation in breast cancer (BC) patients is the potential for tumor contamination in the transplanted product. We present a patient with advanced disease who received high-dose chemotherapy (HDC) and PBPC support as consolidation therapy after achieving complete remission with standard-dose first-line treatment, and suffered recurrence of the disease 6 months after transplantation. Retrospective analysis revealed the presence of contaminating cells in the leukapheretic product, and clinical evidence suggested a role for these cells in the tumor relapse.

Antineoplastic Combined Chemotherapy Protocols↗

Grand multiparity: a study of 168 cases.

The aim of this retrospective study was to consider the problem of grand multiparity in our female population to evaluate if grand multiparity represents a real risk factor for pregnancy, delivery and fetal well-being. From 1981 to 1989 the Gynaecology and Obstetrics Institute of Turin University together with St. Anna Hospital of Turin carried out a retrospective study on pregnancy course, delivery and fetal status in 168 women who had had four or more pregnancies and in 5320 multiparous women who had parity < 4. We analyzed the parity distribution in the different ages with the aid of the registry office and by consulting patient's obstetric clinical history. We evaluated the incidence of gestational complications in the multiparous group. Finally we studied the delivery modality and perinatal mortality in 72,907 births from 1981 to 1989.

Adult↗

Complications of pelvic and para-aortic lymphadenectomy in patients with endometrial cancer.

The International Federation of Gynecology and Obstetrics (FIGO) changed the staging criteria for endometrial cancer in 1988 and adopted a surgical-pathological staging involving also pelvic and/or para-aortic lymphadenectomy. A total of 236 patients were treated for endometrial adenocarcinoma at Department B of the Gynecologic and Obstetrics Institute, University of Turin, between January 1976 and December 1995. Our protocol for surgical staging always entails pelvic and para-aortic lymphadenectomy and a simple total hysterectomy and bilateral adnexectomy with removal of the upper third of the vagina. The aim of this study was to carry out a retrospective evaluation of the morbidity in patients with endometrial cancer after surgical treatment, either TAH-BSO alone or TAH-BSO with pelvic and para-aortic lymphadenectomy.

Adenocarcinoma↗

Urinary endothelin excretion in patients with acute lung injury.

Increase in circulating levels of endothelin (ET), a potent vasoconstrictive and mitogenic endothelium-derived peptide, has been proposed as a marker of endothelium dysfunction in acute lung injury (ALI). In the present study, we have measured levels of immunoreactive ET (irET) by radioimmunoassay, in arterial (irETart), venous (irETven) and urine (irETur) samples obtained from 10 patients with ALI and 10 healthy volunteers. Arterovenous ratio, 24 h urine excretion and renal clearance of the peptide were calculated, to obtain indices of endogenous ET metabolism. The arterovenous ratio of irET was significantly higher in patients with ALI than in healthy volunteers (1.20 +/- 0.20 and 0.85 +/- 0.06, respectively; p < 0.05)). Twenty four hour urinary excretion of the peptide was increased in patients with ALI as compared to healthy volunteers (134.10 +/- 21.0 and 71.70 +/- 9.30 ng.24 h-1, respectively; p < 0.001). Renal clearance of irET was similar in patients with ALI and healthy volunteers, indicating that the increase in excretion as well as in arterovenous gradient observed in patients with ALI was related mainly to pulmonary abnormalities of peptide handling. Urinary excretion of endothelin might be a useful marker of endothelial dysfunction occurring in acute lung injury.

Adult↗

Cervical cerclage for malformed uterus.

The role of cervical cerclage was evaluated in six pregnant women with anomalous uterus. Early prophylactic cerclage according to the Shirodkar and McDonald technique was done on all cases of uterine malformation (except septate uterus) with or without cervical incompetence in association with progesterone and antispastic therapy. Improvement in obstetrical outcome was noted after cerclage. Even if no doubt exists as to the need for cerclage in cases of cervical incompetence, the concept of routine prophylactic cerclage in all cases of uterine anomalies should be considered.

Abortion, Habitual↗

Tamoxifen and endometrial cancer: new data for an old problem. Review.

Tamoxifen, a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Data on a possible association of endometrial pathologies with Tamoxifen treatment have been accumulating. The current literature and our experience are presented.

Antineoplastic Agents, Hormonal↗