Recombinant Collagen Engineered to Bind to Discoidin Domain Receptors Functions as a Receptor Inhibitor

A bacterial collagen-like protein Scl2 has been developed as a recombinant collagen model system to host human collagen ligand-binding sequences, with the goal of generating biomaterials with selective collagen bioactivities. Defined binding sites in human collagen for integrins, fibronectin, heparin, and MMP-1 have been introduced into the triple-helical domain of the bacterial collagen and led to the expected biological activities. The modular insertion of activities is extended here to the discoidin domain receptors (DDRs), which are collagen-activated receptor tyrosine kinases. Insertion of the DDR-binding sequence from human collagen III into bacterial collagen led to specific receptor binding. However, even at the highest testable concentrations, the construct was unable to stimulate DDR autophosphorylation. The recombinant collagen expressed in Escherichia coli does not contain hydroxyproline (Hyp), and complementary synthetic peptide studies showed that replacement of Hyp by Pro at the critical Gly-Val-Met-Gly-Phe-Hyp position decreased the DDR-binding affinity and consequently required a higher concentration for the induction of receptor activation. The ability of the recombinant bacterial collagen to bind the DDRs without inducing kinase activation suggested it could interfere with the interactions between animal collagen and the DDRs, and such an inhibitory role was confirmed in vitro and with a cell migration assay. This study illustrates that recombinant collagen can complement synthetic peptides in investigating structure-activity relationships, and this system has the potential for the introduction or inhibition of specific biological activities

Oncoplastic and reconstructive surgery in SENONETWORK Italian breast centers: lights and shadows

Highlights: • Despite the significance of oncoplastic procedure, an italian database is lacking. • Senonetwork established a multidisciplinary survey to assess their safety and efficacy. • Reconstructive outcomes were positive across low and high-volume centers. • After mastectomy, implant-based techniques are common. DTI reconstruction is advantageuos. • This contributes to the global understanding of effective strategies against breast cancer

Bone marrow microenvironment of MPN cells

In this chapter, we will discuss the current knowledge concerning the alterations of the cellular components in the bone marrow niche in Myeloproliferative Neoplasms (MPNs), highlighting the central role of the megakaryocytes in MPN progression, and the extracellular matrix components characterizing the fibrotic bone marrow

Constitutive STAT5 phosphorylation in CD34+ cells of patients with primary myelofibrosis: Correlation with driver mutation status and disease severity

Primary Myelofibrosis (PMF) is a myeloproliferative disorder associated with JAK2V617F, Calreticulin (CALR) indels, and MPLW515L/K mutations activating the tyrosine kinase JAK2 and its downstream signaling pathway. The nature of signaling abnormalities in primary cells from PMF patients is poorly understood, since most of the work has been performed in cell lines or animal models. By flow cytometry we measured constitutive and cytokine induced phosphorylation of STAT5, STAT3, and ERK1/2 in circulating CD34+ cells from 57 patients with PMF (20 with prefibrotic-PMF) and 13 healthy controls (CTRLs). Levels of constitutive and TPO induced p-STAT5, and IL6 induced p-STAT3 were higher in patients than in CTRLs. Constitutive p-STAT5 values were lower in CALR than homozygous JAK2V617F mutated CD34+ cells from PMF patients. Moreover, constitutive p-STAT5 and IL6 induced p-STAT3 values correlated directly with circulating CD34+ cell number/L, and inversely with the frequency of circulating CD34+ cells expressing CXCR4. Constitutive p-STAT5 values of CD34+ cells were also inversely correlated with hemoglobin levels. When the patients were divided according with presence/absence of JAK2V617F mutation, all the correlations described characterized the JAK2V617F+ patients with prefibrotic-PMF (P-PMF). In conclusion, increased constitutive p-STAT5 and IL6 induced p-STAT3 values in circulating CD34+ cells characterize patients with PMF. Constitutive p-STAT5 and IL6 induced p-STAT3 values correlate with circulating CD34+ cell number/L, the frequency of circulating CD34+ cells expressing CXCR4 and hemoglobin levels within the prefibrotic JAK2V617F+ patient population. Our data point toward a complex activation of STAT5-dependent pathways in the stem/progenitor cell compartment, that characterize the phenotypic diversity of PMF

Destructive, multifocal squamous-cell carcinoma nodules on the cheecks and neck of an elderly woman with a dementia syndrome

Introduction: Squamous-cell carcinoma is the second most common form of skin cancer. It can develop on normal skin, actinic keratoses, leukoplakia, and burn scars. The tumor is characterized by remarkable variability at the macroscopic and histopathologic levels. Case report: A 93-year-old woman was admitted to nursing home with a diagnosis of dementia syndrome and squamous cell nodular carcinoma on cheeks and neck region. The physical examination revealed firm, black excrescences with irregular surfaces over both cheekbones, which were roughly the size of hazelnuts. Similar nodules were present with ulcers on other areas of the face. The patient was admitted to the day hospital twice for wide excision of the tumors in the zygomatic region. Later, the neck tumors were removed, and the wound was repaired with a rotation flap after careful control of bleeding. For the latter surgery, the patient was hospitalized for a few days in a geriatric ward to ensure optimal medical care and psychological support. The histological examination revealed ulcerated, well-differentiated squamous-cell carcinoma that extended down to the subcutaneous layer. Shortly after surgery, she returned to the nursing home to resume rehabilitation and group therapy

Destructive, multifocal squamous-cell carcinoma nodules on the cheecks and neck of an elderly woman with a dementia syndrome

Introduction: Squamous-cell carcinoma is the second most common form of skin cancer. It can develop on normal skin, actinic keratoses, leukoplakia, and burn scars. The tumor is characterized by remarkable variability at the macroscopic and histopathologic levels. Case report: A 93-year-old woman was admitted to nursing home with a diagnosis of dementia syndrome and squamous cell nodular carcinoma on cheeks and neck region. The physical examination revealed firm, black excrescences with irregular surfaces over both cheekbones, which were roughly the size of hazelnuts. Similar nodules were present with ulcers on other areas of the face. The patient was admitted to the day hospital twice for wide excision of the tumors in the zygomatic region. Later, the neck tumors were removed, and the wound was repaired with a rotation flap after careful control of bleeding. For the latter surgery, the patient was hospitalized for a few days in a geriatric ward to ensure optimal medical care and psychological support. The histological examination revealed ulcerated, well-differentiated squamous-cell carcinoma that extended down to the subcutaneous layer. Shortly after surgery, she returned to the nursing home to resume rehabilitation and group therapy

Are mesh anchoring sutures necessary in ventral hernioplasty? Multicenter study

Background: Avoiding mesh fixation to the surrounding tissue in ventral hernioplasty would simplify the operation, decrease the time of the procedure, and decrease the risk of suture-related complications. Methods: Four hospitals included 111 patients according to the common protocol for prospective clinical evaluation of sutureless ventral hernioplasty. Surgical technique involves placement of the polypropylene mesh with flat-shape memory in either the retromuscular or preperitoneal space without suture anchoring. Results: Local complication rate was low (12.6%, 14 patients), postoperative pain measured according to the visual analogue scale was minimal (mean 4, range 1-8). Three recurrences (3%) were recorded. Mild scar discomfort, which did not require treatment nor limit physical activity, was recorded in 28 (25%), 18 (17%), and 11 (14%) patients at 6-month, 1- and 2-year follow-up, respectively. Conclusions: Results ofthe study suggest that the sutureless sublay technique is safe and effective in the treatment of ventral abdominal hernia, especially in small and medium defects. © Springer-Verlag 2007

Are mesh anchoring sutures necessary in ventral hernioplasty? Multicenter study

Background: Avoiding mesh fixation to the surrounding tissue in ventral hernioplasty would simplify the operation, decrease the time of the procedure, and decrease the risk of suture-related complications. Methods: Four hospitals included 111 patients according to the common protocol for prospective clinical evaluation of sutureless ventral hernioplasty. Surgical technique involves placement of the polypropylene mesh with flat-shape memory in either the retromuscular or preperitoneal space without suture anchoring. Results: Local complication rate was low (12.6%, 14 patients), postoperative pain measured according to the visual analogue scale was minimal (mean 4, range 1-8). Three recurrences (3%) were recorded. Mild scar discomfort, which did not require treatment nor limit physical activity, was recorded in 28 (25%), 18 (17%), and 11 (14%) patients at 6-month, 1- and 2-year follow-up, respectively. Conclusions: Results ofthe study suggest that the sutureless sublay technique is safe and effective in the treatment of ventral abdominal hernia, especially in small and medium defects. © Springer-Verlag 2007

Folic acid-conjugated 4-amino-phenylboronate, a boron-containing compound designed for boron neutron capture therapy, is an unexpected agonist for human neutrophils and platelets

Boron neutron capture therapy (BNCT) is an anti-cancer treatment based on the accumulation in the tumor cells of 10B-containing molecules and subsequent irradiation with low energy neutrons, which bring about the decay of 10B to very toxic 7Li3+ and 4He2+ ions. The effectiveness of BNCT is limited by the low delivery and accumulation of the used 10B-containing compounds. Here we report the development of folic acid-conjugated 4-amino-phenylboronate as a novel possible compound for the selective delivery of 10B in BNCT. An extensive analysis about its biocompatibility to mature blood cells and platelet progenitors revealed that the compound markedly supports platelet aggregation, neutrophil oxidative burst and inhibition of megakaryocyte development, while it does not have any effect on red blood cells