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Biomedical subjects

C Palmieri

Publications and source records attributed to C Palmieri.

At least 19 recordsLinked to original sources
PubMed2007

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

Adult↗
PubMed2006

Immunohistochemical characterization of Kisselev nodules (ectopic lymphoid follicles) in wild boar (Sus scrofa L.).

This paper describes the histopathological features and cellular distribution of T lymphocytes (CD3), B cells (CD79), follicular dendritic cells (FDC) and macrophages (alpha-1-antitrypsin, lysozyme) in lymphoid aggregates (Kisselev nodules) found in the lung, kidney and liver of wild boar (Sus scrofa L.). The distribution of immunoreactive cells, tested for antibodies, was similar to that found in the cortex of lymph nodes: lymphoid follicles with germinal centers mainly consisting of CD79+ B cells with sparse interfollicular tissue (CD3+ T lymphocytes). This finding and the association of these structures with helminthic infections suggests that local humoral immunity is central to the organism's response to parasitic challenge. The presence of follicular dendritic cells confirms the high degree of organization of these lymphoid-like structures. The role of other pathogenic factors and the induction of chronic inflammatory reaction in these ectopic lymphoid sites is also discussed.

Animals↗
PubMed2006

AIDS-related non-Hodgkin's lymphoma in the first decade of highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) has had a dramatic effect on the natural history of HIV disease, reducing the incidence of opportunistic infections and Kaposi's sarcoma, and improving overall survival. Since HAART became available in 1996, the incidence of AIDS-related non-Hodgkin's lymphoma (NHL) has fallen, and although there has been no change in the clinical features at presentation, the overall survival of patients with AIDS-related NHL has improved. Prognosis is now determined chiefly by lymphoma-associated factors similar to those in the general population (the International Prognostic Index), although serum CD4 count at lymphoma diagnosis is an additional independent prognostic factor. The management of patients with AIDS-related NHL with either infusional chemotherapy or CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine and prednisolone) achieves response and survival rates approaching those observed in the general population. However, careful attention should be paid to central nervous system chemoprophylaxis, opportunistic infection prophylaxis and potential drug interactions between cytotoxic and antiretroviral therapies. In the era of HAART, the goal of therapy for these patients is now complete remission rather than palliation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Placental abnormalities in ovine somatic cell clones at term: a light and electron microscopic investigation.

To investigate the reasons for fetal losses after somatic cell nuclear transfer, an immunohistochemical and ultrastructural analysis of cloned placentae was performed. The main features observed were a marked reduction of villous vascularization, hypoplasia of trophoblastic epithelium, lack of binucleate cells, immaturity of placental vessels and reduced vasculogenesis. By means of transmission electron microscopy (TEM), a diffuse thickening and lamination of subtrophoblastic basement membrane (SBM) were noted in cloned placentae. These results led us to hypothesize, through an autoamplification model, that the abnormal vascularization, the ischaemia and the low development of an high specialized trophoblastic epithelium were the primary causes of the fetal loss occurring after somatic cells nuclear transfer.

Animals↗
PubMed2006

Serum 25-hydroxyvitamin D levels in early and advanced breast cancer.

BACKGROUND: Laboratory and epidemiological studies have implicated vitamin D deficiency in the pathogenesis of breast cancer. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D) promotes differentiation and apoptosis, and potently inhibits proliferation of malignant breast epithelial cells in culture. Serum levels of 1,25(OH)(2)D are higher in normal women than in patients with primary breast cancer. AIM: To clarify the role of vitamin D in breast cancer progression by comparing the levels of serum vitamin D in patients with early and in those with advanced breast cancer. METHODS: Circulating levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 women with early-stage disease and 75 women with locally advanced or metastatic disease. RESULTS: Patients with early-stage breast cancer had significantly higher circulating levels of 25(OH)D (p<0.005) and significantly lower PTH (p<0.001) levels than those with advanced disease. Calcium levels did not differ significantly (p = 0.74). CONCLUSION: Serum levels of 25(OH)D are significantly higher in patients with early-stage breast cancer than in those with locally advanced or metastatic disease.

Adult↗
PubMed2006

Partial purification and MALDI-TOF MS analysis of UN1, a tumor antigen membrane glycoprotein.

UN1 is a membrane glycoprotein that is expressed in immature human thymocytes, a subpopulation of peripheral T lymphocytes, the HPB acute lymphoblastic leukemia (ALL) T-cell line and fetal thymus. We previously reported the isolation of a monoclonal antibody (UN1 mAb) recognizing the UN1 protein that was classified as "unclustered" at the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. UN1 was highly expressed in breast cancer tissues and was undetected in non-proliferative lesions and in normal breast tissues, indicating a role for UN1 in the development of a tumorigenic phenotype of breast cancer cells. In this study, we report a partial purification of the UN1 protein from HPB-ALL T cells by anion-exchange chromatography followed by immunoprecipitation with the UN1 mAb and MALDI-TOF MS analysis. This analysis should assist in identifying the amino acid sequence of UN1.

Antigens, Neoplasm↗
PubMed2006

Pulmonary Kaposi sarcoma in the era of highly active antiretroviral therapy.

OBJECTIVE: Since the introduction of highly active antiretroviral therapy (HAART) there has been a dramatic reduction in the incidence of Kaposi sarcoma (KS) and an improvement in survival. We wished to examine whether the outcome in pulmonary KS (pKS) has also altered. METHODS: In a single-institution cohort of 1140 HIV-positive patients with KS, 305 patients were diagnosed in the HAART era (1996-2004). We examined the clinicopathological features and outcomes of these patients, of whom 25 had pKS and 280 did not. RESULTS: Patients with pKS had lower CD4 cell counts at the time of KS diagnosis (Mann-Whitney U-test P=0.005). The incidence of pKS was higher in African patients than in non-African patients in this sample (Fisher's test, P=0.001). There were no significant differences in age, gender, plasma HIV-1 viral load or prior HAART treatment at the time of KS diagnosis. Five-year overall survival in the pKS group was 49% [95% confidence interval (CI) 26-73%] as compared with 82% (95% CI 76-87%) for the non-pKS group (log rank, P<0.0001). CONCLUSION: PKS remains an ominous diagnosis in the era of HAART, with a median survival of just 1.6 years.

AIDS-Related Opportunistic Infections↗
PubMed2005

The presentation and survival of patients with non-cutaneous AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immune deficiency syndrome related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe for the first time a proportion of patients with AIDS-KS who presented with no evidence of cutaneous disease. PATIENTS AND METHODS: From our cohort of 5932 individuals infected with the human immunodeficiency virus (HIV-1) treated in the HAART era, 319 were identified with KS. Of these, 11 patients (5.4%) were diagnosed with KS without the presence of any cutaneous disease. We compared their survival, clinical, immunological and virological characteristics to other individuals with KS. RESULTS: There were no statistically significant differences in survival, CD4 count or HIV viral load at KS presentation. We observed that tumour-associated oedema (P = 0.046) and non-oral gastrointestinal KS (P = 0.042) were significantly more common in patients with non-cutaneous KS. Only one case of non-cutaneous KS was observed prior to the era of highly active anti-retroviral therapy (HAART). CONCLUSIONS: Non-cutaneous KS is a recognisable condition; patients should be treated with the standard of care as their prognosis is not inferior. This is likely to reflect a strong immune response, in the era of HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Spontaneous ocular squamous cell carcinoma in twin goats: pathological and biomolecular studies.

Ocular squamous cell carcinoma (OSCC) is a well-characterized tumour occurring spontaneously in cattle and other mammalian species but not previously reported in the goat. This report describes the histological features of well-differentiated OSCCs in twin goats. Biomolecular investigations led to the identification of Papillomavirus-related DNA sequences within the neoplastic ocular parenchyma of both animals, but immunohistochemical and ultrastructural studies failed to demonstrate viral particles. A putative role of Papillomavirus in the aetiology of OSCC is discussed, together with other possible causative factors.

Animals↗
PubMed2004

Managing malignant disease in patients with porphyria.

Certain types of porphyria have an increased incidence of malignant disease. In addition, patients with all forms of porphyria may develop malignant disease as a 'normal life event'. The investigation and treatment of porphyric patients with malignant disease requires specific precautions to minimize the risk of an acute porphyric attack, and to ensure optimum treatment of the malignancy. We briefly review the biochemical basis, clinical features and current management of porphyria in cancer patients.

Antineoplastic Agents↗
PubMed2004

The expression of oestrogen receptor (ER)-beta and its variants, but not ERalpha, in adult human mammary fibroblasts.

Whilst oestrogen receptor (ER)-alpha and ERbeta have been shown to be important in the development of the mammary gland, the cell-specific expression pattern of these two receptors within the human breast is not clear. Although it is well established that in the developing rodent mammary gland stromal ERalpha mediates the secretion of growth factors which stimulate the proliferation of the ductal epithelium, the expression of ERalpha in human adult breast stromal fibroblasts is controversial, and the expression of ERbeta has not been properly defined. In the present study, we have evaluated the expression of ERalpha and ERbeta by immunohistochemistry in normal tissue samples, and in purified human breast fibroblasts by Western blotting, RT-PCR analysis and ligand-binding sucrose gradient assay. Our data clearly demonstrated that ERbeta variants, including ERbeta1, ERbeta2, ERbeta5, ERbetadelta and ERbetains, but not ERalpha, are expressed in human adult mammary fibroblasts. These results are supported by the findings that an ERbeta-selective ligand, BAG, but not the ERalpha high-affinity ligand oestradiol, can induce fibroblast growth factor-7 release and activate transcription from an oestrogen-responsive element promoter in these adult human mammary fibroblasts. Together, these observations revealed that, in the adult breast and in breast cancer, the proliferative signals derived from the stroma of adult mammary glands in response to oestrogen are not mediated by ERalpha and provide new insights into the nature of stromal-epithelial interactions in the adult mammary gland. In addition, the expression of these ERbeta variants in cells where there is no ERalpha suggested that these ERbeta splice forms may have functions other than that of modulating ERalpha activity.

Animals↗
PubMed2003

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro.

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic death of PC cells. The proapoptotic effect was correlated to cleavage/activation of caspase-9 and poly(ADP)-ribose polymerase, but not of caspase-3. Moreover, we studied the p21(ras) signalling in cells exposed to ZOL and detected a reduction of p21(ras) and Raf-1 content and functional downregulation of the terminal enzyme ERK/MAPkinase and of the pKB/Akt survival pathway. Finally, we observed that ZOL induces significant cytoskeletal rearrangements. In conclusion, we demonstrated that ZOL induces growth inhibition and apoptosis on PC cells and interferes with growth and survival pathways downstream to p21(ras). These findings might be relevant for expanding application of BPs in cancer treatment.

Apoptosis↗
PubMed2003

Resolution of late-onset asthma following high-dose chemotherapy.

We describe a patient with moderately severe (British Thorax Society Step IV/V) asthma requiring regular inhaled and oral corticosteroids to control symptoms who experienced resolution of her asthma following high-dose chemotherapy and autologous stem cell transplantation for breast cancer. As far as the authors are aware this is the first reported case.

Antibiotics, Antineoplastic↗
PubMed2003

Fibroblast growth factor 7, secreted by breast fibroblasts, is an interleukin-1beta-induced paracrine growth factor for human breast cells.

Keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF7) is known to be a potent growth factor for mammary cells but its origin, cellular targets and mode of action in the breast are unclear. In this study, we carried out studies to determine the localisation of FGF7 and its receptor, and the related growth factor FGF10. We also determined the factors that regulate FGF7 release from stromal cells and the effects of FGF7 on normal and neoplastic breast cells. Using an FGF7-specific antibody which does not react with the FGF7 heparan sulphate proteoglycan (HSPG)-binding site, we showed epithelial and myoepithelial immunohistochemical staining in normal breast sections, and epithelial staining in breast carcinomas. Stromal staining was also detected in some lobular carcinomas as well as a subset of invasive ductal carcinomas. FGF10 and FGF receptor (FGFR)2 immunostaining showed a similar epithelial expression pattern, whereas no stromal staining was observed. We purified normal breast stromal, epithelial and myoepithelial cells and showed that FGF7 stimulated proliferation of both epithelial cell types, but not stromal fibroblasts. We also examined the effects of FGF7 on Matrigel-embedded organoids, containing both epithelial and myoepithelial cells, and showed FGF7 induced an increase in cellular proliferation. Furthermore, conditioned medium derived from stromal cells was shown to increase the proliferation of normal and neoplastic breast epithelial cells, which could be abolished by a neutralising antibody to FGF7. Finally, we showed that interleukin-1beta, but not oestradiol or other oestrogen receptor ligands, caused a dose-related FGF7 release. Further results also indicate that the epithelial localisation of FGF7 and FGF10 in breast tissue sections is likely to be due to their binding to their cognate receptor. In summary, our findings suggest that FGF7 is a paracrine growth factor in the breast. FGF7 is produced by the breast stromal fibroblasts and has profound proliferative and morphogenic roles on both epithelial and myoepithelial cells.

Blotting, Western↗
PubMed2002

Oxaliplatin (L-OHP) treatment of human myeloma cells induces in vitro growth inhibition and apoptotic cell death.

Oxaliplatin (L-OHP), a diaminocyclohexane platinum derivative, is an active and well tolerated anticancer drug which is presently used in the treatment of gastrointestinal tumours. Since the efficacy of L-OHP in the treatment of multiple myeloma (MM) has not yet been evaluated, we studied the antiproliferative activity of this compound in vitro in a panel of MM cell lines (XG1, XG1a, U266 and IM-9). We found that L-OHP inhibited the growth of MM cells at therapeutically achievable concentrations (IC(50): 5-10 microM after 24 h of exposure) and was more active than Cisplatin (CDDP) or Carboplatin (CBDCA). The activity of L-OHP was apparently not affected by interleukin-6 (IL-6), the major growth and survival factor of MM cells. We also found that L-OHP induced apoptotic cell death. We demonstrated that the combination of L-OHP with Dexamethasone (Dex) resulted in the enhancement of the anti-myeloma effects. L-OHP and Dex both induced poly adenosine diphosphate (ADP)-ribose polymerase (PARP) cleavage and this induction was enhanced by the combined treatment. L-OHP-induced apoptosis correlated with caspase-3 cleavage, but this correlation could not be demonstrated in Dex-treated cells. Taken together, these in vitro results provide a rationale for the experimental use of L-OHP in the treatment of MM patients and suggest therapeutic combinations of potential value.

Antineoplastic Agents↗
PubMed2002

Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis.

OBJECTIVE: To describe the treatment of polymyositis (PM) and dermatomyositis (DM) with prednisone (PRED) and cyclosporin A (CSA) alone or associated with intravenous immunoglobulin (IVIg) and plasmapheresis (PEX). METHODS: Between 1992 and 1999 CSA and PRED were used to treat 20 patients with idiopathic myositis (12 with DM, eight with PM), diagnosed according to the Bohan and Peter criteria. In patients with refractory or relapsed disease, IVIg was added alone (seven cases) or synchronised with PEX (six cases). A standardised protocol was used to evaluate the patients, and assess disease activity and treatment response. RESULTS: Despite a transient response to PRED and CSA in 16/20 cases, this combination did not induce full remission in 13/20 cases, which led to the IVIg trial with or without PEX. Patients receiving PRED and CSA plus IVIg had a significantly higher probability of maintaining complete remission at the end of the four year follow up period than those treated with PRED and CSA alone (p<0.001). No further benefit was added by the PEX. The presence of arthritis significantly correlated with a poorer response to treatment (p<0.05). Adverse effects were gingival hyperplasia (one patient) and transient renal dysfunction (one). CONCLUSIONS: This open study suggests that combined treatment with PRED, CSA, and IVIg is useful in patients with myositis, even those with refractory or relapsed disease; no increase in the number or type of side effects is seen.

Adult↗
PubMed2002

Estrogen receptor beta in breast cancer.

Estrogen is essential for normal growth and differentiation in the mammary gland. It also supports growth of approximately 50% of primary breast cancers. For this reason, removal of estrogen or blocking of its action with the anti-estrogen, tamoxifen, is the main treatment for estrogen receptor alpha (ERalpha)-positive tumors. In 1996, when oncologists became aware of a second ER, ERbeta, there was some doubt as to whether this receptor would be of importance in breast cancer because the clinical consensus was that responsiveness to tamoxifen is related to the presence of ERalpha in breast cancer. Today we know that ERalpha and ERbeta have distinct cellular distributions, regulate separate sets of genes and can oppose each other's actions on some genes. We also know that ERbeta is widely expressed in both the normal and malignant breast and that there are proliferating cells in the breast which express ERbeta. In this review we summarize what is known about ERbeta in breast cancer and examine the possibility that ERbeta-selective ligands may well represent a useful class of pharmacological tools with a novel target, namely proliferating cells expressing ERbeta.

Animals↗