Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

<p>Abstract</p> <p>Background</p> <p>Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-<it>ras </it>mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.</p> <p>Methods</p> <p>Cytokine determinations were performed by commercially available ELISA kits, while K12-<it>ras </it>mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.</p> <p>Results</p> <p>Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-<it>ras </it>mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.</p> <p>Conclusion</p> <p>IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.</p

The lungs and platelet production

Several studies have suggested that thrombopoiesis may occur in the lungs. To investigate the role of the lungs in platelet production, we measured automated platelet parameters in blood from the pulmonary artery and the radial artery (n ¼ 125) or aorta (n ¼ 26) in patients undergoing aorto-coronary bypass. No significant differences were found between pulmonary and radial arterial blood with regard to platelet count (192.132 ± 46.250 vs. 192.004 ± 46.294 · 109/l), mean platelet volume (11.03 ± 1.04 vs. 11.03 ± 1.03 fl), plateletcrit (0.212 ± 0.051 vs. 0.212 ± 0.051 · 10)2), platelet distribution width (14.48 ± 2.16 vs. 14.47 ± 2.08 fl) and platelet–large cell ratio (0.350 ± 0.076 vs. 0.351 ± 0.078). Similar results were obtained in comparisons between pulmonary arterial and aortic blood. A coefficient of linear correlation of 0.98 was found between the pulmonary and radial arterial and aortic platelet counts. These findings suggest that the platelet population entering the lungs was the same as the platelet population leaving them. Our results do not therefore support the theory of pulmonary platelet production. Keywords Platelet production, lungs, arterial platelet counts, aortic platelet count

AUTOIMMUNE THROMBOCYTOPENIC PURPURA ASSOCIATED WITH DIFFERENT FORMS OF CANCER

Twenty-two patients with autoimmune thrombocytopenic purpura (ATP) associated with different forms of neoplasms are presented. Cancer-related ATP appeared at the time of either the clinical manifestation or relapse of the neoplastic disease, sometimes one month to 10 years after surgery and/or radio-or chemotherapy. All the patients presented high levels of both platelet-associated IgG and less frequently of serum-platelet bindable IgG. The surgical removal of the tumor performed in some thrombocytopenic patients did not induce the remission of ATP. The clinical and hematological response to steroid therapy was generally poor. The possibility of an occult tumor in patients with apparently idiopathic ATP and the possible autoimmune etiology of thrombocytopenia in cancer should therefore be considered, although the pathogenetic mechanisms of autoimmune diseases in neoplastic patients have not yet been well defined

Involvment of bcl-2 and bax gene expression in apoptosis and differentiation of the non-tumorigenic murine hematopoietic cell line, 32DCl3(G).

32DCl3(G) is an interleukin-3 (IL-3) dependent, non-tumorigenic murine hematopoietic cell line which undergoes terminal differentiation into granulocytes when exposed to granulocyte-colony stimulating factor (G-CSF). This line therefore offers a convenient system to study the expression of genes involved in apoptosis and differentiation. In our experiments we have acquired evidence that during the differentiation pathway, likewise in apoptosis induced by IL-3 deprivation, detectable levels of bax mRNA appear, while bcl-2 expression decreases. These events are under the control of the p53 tumor-suppressor gene. In these cells, an overexpression of exogenous wild-type p53 leads to a decrease in bcl-2 mRNA and to the appearance of box mRNA, which instead is absent in the parental cells growing in IL-3 conditioned medium. Furthermore, results from experiments on p53 transfected cells demonstrate that excess wild-type p53 activity, on its own, fails to elicit apoptosis as long as IL-3 is present and does not induce differentiation if G-CSF is not added to the culture medium. We conclude that in apoptosis and differentiation of 32DCl3(G) the alterate ratio of bcl-2 and box gene expression, modulated by p53, is an early event dependent on IL-3 withdrawal and that the appearance of bax and the decrease of bcl-2 expression are necessary, but not sufficient for the acquisition of a completely mature granulocytic phenotype

Delayed colorectal cancer care during covid-19 pandemic (decor-19). Global perspective from an international survey

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care