Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells.

The colony-stimulating factor-1 (CSF-1) and its receptor CSF-1R physiologically regulate the monocyte/macrophage system, trophoblast implantation and breast development. An abnormal CSF-1R expression has been documented in several human epithelial tumors, including breast carcinomas. We recently demonstrated that CSF-1/CSF-1R signaling drives proliferation of breast cancer cells via 'classical' receptor tyrosine kinase signaling, including activation of the extracellular signal-regulated kinase 1/2.

AML1/ETO sensitizes via TRAIL acute myeloid leukemia cells to the pro-apoptotic effects of hypoxia.

We determined the effects of severe hypoxia (∼0.1% O2) on acute myeloid leukemia cells expressing the AML1/ETO oncogene. Incubation of Kasumi-1 cells in hypoxia induced growth arrest, apoptosis and reduction of AML1/ETO protein expression.

Time- and residue-specific differences in histone acetylation induced by VPA and SAHA in AML1/ETO-positive leukemia cells.

We analyzed the activity of the histone deacetylase inhibitor (HDACi) suberoyl-anilide hydroxamic acid (SAHA) on Kasumi-1 acute myeloid leukemia (AML) cells expressing AML1/ETO. We also compared the effects of SAHA to those of valproic acid (VPA), a short-chain fatty acid HDACi. SAHA and VPA induced histone H3 and H4 acetylation, myeloid differentiation and massive early apoptosis.

The colony-stimulating factor-1 (CSF-1) receptor sustains ERK1/2 activation and proliferation in breast cancer cell lines.

Breast cancer is the second leading cause of cancer-related deaths in western countries. Colony-Stimulating Factor-1 (CSF-1) and its receptor (CSF-1R) regulate macrophage and osteoclast production, trophoblast implantation and mammary gland development. The expression of CSF-1R and/or CSF-1 strongly correlates with poor prognosis in several human epithelial tumors, including breast carcinomas.

Hypoxia selects bortezomib-resistant stem cells of chronic myeloid leukemia.

We previously demonstrated that severe hypoxia inhibits growth of Chronic Myeloid Leukemia (CML) cells and selects stem cells where BCR/Abl(protein) is suppressed, although mRNA is not, so that hypoxia-selected stem cells, while remaining leukemic, are independent of BCR/Abl signaling and thereby refractory to Imatinib-mesylate. The main target of this study was to address the effects of the proteasome inhibitor Bortezomib (BZ) on the maintenance of stem or progenitor cells in hypoxic primary cultures (LC1), by determining the capacity of LC1 cells to repopulate normoxic secondary cultures (LC2) and the kinetics of this repopulation. Unselected K562 cells from day-2 hypoxic LC1 repopulated LC2 with rapid, progenitor-type kinetics; this repopulation was suppressed by BZ addition to LC1 at time 0, but completely resistant to day-1 BZ, indicating that progenitors require some time to adapt to stand hypoxia.

Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate.

Background: Incubation of chronic myeloid leukemia cells in hypoxia inhibits growth and selects BCR/Abl-independent cells with stem cell properties which are refractory to imatinib-mesylate. This study aimed to characterize the relationship of this refractoriness with glucose availability in the environment.

Design And Methods: K562 or primary chronic myeloid leukemia cells were cultured at 0.

ERK5/BMK1 is indispensable for optimal colony-stimulating factor 1 (CSF-1)-induced proliferation in macrophages in a Src-dependent fashion.

CSF-1, by binding to its high-affinity receptor CSF-1R, sustains the survival and proliferation of monocyte/macrophages, which are central cells of innate immunity and inflammation. The MAPK ERK5 (also known as big MAPK-1, BMK1, or MAPK7) is a 98-kDa molecule sharing high homology with ERK1/2. ERK5 is activated by oxidative stress or growth factor stimulation.

Severe hypoxia defines heterogeneity and selects highly immature progenitors within clonal erythroleukemia cells.

We showed that resistance to severe hypoxia defines hierarchical levels within normal hematopoietic populations and that hypoxia modulates the balance between generation of progenitors and maintenance of hematopoietic stem cells (HSC) in favor of the latter. This study deals with the effects of hypoxia (0.1% oxygen) in vitro on Friend's murine erythroleukemia (MEL) cells, addressing the question of whether a clonal leukemia cell population comprise functionally different cell subsets characterized by different hypoxia resistance.

The c-Jun-N-terminal-Kinase inhibitor SP600125 enhances the butyrate derivative D1-induced apoptosis via caspase 8 activation in Kasumi 1 t(8;21) acute myeloid leukaemia cells.

We recently showed that the histone deacetylase inhibitor D1 induced apoptosis in the t(8;21) Kasumi 1 acute myeloid leukaemia (AML) cell line and activated caspase 9. The present study characterised the effects of the combined administration of D1 with PD98059, SB203580 or SP600125, specific inhibitors of mitogen-activated protein kinase, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 or Jun N-terminal kinase (JNK), respectively. Among these inhibitors, SP600125 was the only one to markedly induce apoptosis and decrease cell proliferation.

Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF.

The macrophage colony-stimulating factor (M-CSF, CSF-1) regulates survival, proliferation and differentiation of mononuclear phagocytes, as well as macrophage motility and morphology. The latter features are usually regulated by ECM-mediated activation of integrins and subsequent tyrosine phosphorylation of cellular proteins, including focal adhesion kinase (FAK). FAK is phosphorylated by downstream receptor tyrosine kinases as well.

Results of rebiopsy for suspected prostate cancer in symptomatic men with elevated PSA levels.

Aim Of The Study: To develop indications for repeat biopsy in patients with suspected prostate cancer and first negative biopsy.

Materials And Methods: 148 consecutive patients, submitted to two or more biopsies for suspected prostate cancer, were extracted from our database on prostatic diseases. Patients were stratified according to the results of the last biopsy (benign or carcinoma) considering the results of the first and of the last biopsy when more than two biopsies had been performed.

Procollagen type I carboxyterminal extension peptide in serum: a reliable marker of bone metastatic disease in newly diagnosed prostate cancer?

Objective: This study evaluates the accuracy of type I procollagen, a bone matrix glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the results of radionuclide bone scan in newly diagnosed, previously untreated patients with prostate cancer.

Methods: 74 patients underwent serum PSA and procollagen determination using specific antibodies. A staging radionuclide bone scan was then performed; patients with positive bone scan were submitted to x-rays of the suspicious zones.

Serum levels of tumor-associated trypsin inhibitor (TATI) in benign and malignant gynecological diseases.

The behavior of tumor-associated trypsin inhibitor (TATI) as a marker for gynecological cancer was studied in a control population and in patients with different benign and malignant diseases. When a cut-off level of 21.4 micrograms/l was used the specificity was 100% in patients with benign diseases.

[The renin-angiotensin-aldosterone system in liver cirrhosis].

The role of the RAA system in the genesis of ascites in liver cirrhosis patients is not yet perfectly clear. The present study was conducted on 176 cirrhosis patients in order to investigate RAA system function, to assess the changes taking place in the various stages of the disease and to correlate such changes with the various kidney function parameters. The patients were divided into 3 groups as follows: Group I: patients without ascites on admission and with no history of the condition; Group 2: patients with ascites of recent onset and/or response to diuretic treatment; Group 3: patients with ascites not responsive to diuretic treatment.

[Changes in antidiuretic hormone (ADH) in liver cirrhosis with resistant ascites].

The pathogenetic role of ADH in determining hyponatremia in patients with liver cirrhosis is still much debated. Osmotic stimuli are not able to inhibit secretion of ADH in refractory ascites and under such conditions the reduction in effective plasma volume has been put forward as the main cause. Twenty patients with liver cirrhosis and refractory ascites were studied before and during extraction-concentration-reinfusion (ECR) of ascitic fluid by means of Rhodiascit.

[Ferritin, CEA and TPA as tumor markers in breast neoplasms].

In order to assess the sensitivity and specificity of Ferritin, CEA and TPA as neoplastic markers in breast carcinomas, 91 patients all classified according to the TNM-UICC system were studied in a cancer clinic. The results of the analyses indicate that ferritin is apparently only influenced by the presence of metastatic neoplasias and that greater sensitivity is obtained if all three markers are employed simultaneously.

[Advantages of preventing Rh isoimmunization].

The authors analysed the frequency of Rh immunization from 1972 to 1983. The incidence of Rh-immunized women who after the birth of a Rh (D) positive child were not given anti-D immunoglobulin G and in subsequent pregnancies gave birth to a Rh (D) positive child was found to amount to 11.76%, while in women who were given anti-D immunoglobulin D this incidence was 0.

[Study of blood ferritin in cancer patients and its possible use as an indicator of an unfavorable prognosis].

Ferritinaemia levels were measured in 97 neoplastic patients and compared with the levels found in a healthy control group, in order to discover whether ferritinaemia had any significance as a neoplastic marker. Higher levels were encountered in all neoplastic patients (P less than 0.005) than in the control group.

[Evaluation of blood ferritin in sideropenic anemia and its modifications in the course of divided-dose parenteral iron therapy].

Changes in blood ferritin during divided dose parenteral iron therapy and the importance of ferritin evaluation in iron-deficiency anaemia were investigated in 20 women and 10 men with this diagnosis through withdrawals before and after treatment. In 6 subjects, blood ferritin values enabled the presence of iron deficiency to be ruled out, since they were high at the first control (in agreement with the histological examination of the marrow in the search for iron deposits). In sideropenic males, the difference between values at the time of diagnosis and those of normal controls was significant (p less than 0.