Angioleiomyoma of the knee: An uncommon cause of leg pain. A systematic review of the literature

Abstract Objective Angioleiomyoma is a rare benign painful soft tissue tumor, whose knee location is rare. Due its rarity, and not characteristic aspect on MRI the preoperative diagnosis is difficult. Methods We performed a systematic review of the literature, including a case of venous type angioleiomyoma that we have recently managed. Results A total of 24 published papers with 30 cases (including our illustrative case) were identified and included in our review. The mean patient age was 42.3 years (range18-63). The average size of the lesion was 17.8 mm. The presenting symptom was leg pain in 90% of cases. On magnetic resonance imaging (MRI), the lesion appeared isointense in T1 in 80% of cases and hyperintense on T2 in 90% of cases. Avid homogeneous enhancement after gadolinium administration was detected in 94% of cases. All patients underwent surgery and total resection was achieved in 100% of cases. No recurrence was observed after a mean follow-up of 19.5 months. Conclusion Angioleiomyoma occurs rarely in the knee and generally is associated with localized or radiating pain. The preoperative diagnosis is difficult also after completion of MRI study and requires high index of suspicion. Angioleiomyoma widens the spectrum of soft tissue lesions of the extremities and should be included in the differential diagnosis of lesions in this area

Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1

Aims. The aims of this study were to evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and to investigate their relevant molecular mechanisms. Methods. Human endothelial cells (HMVEC-d, HUVEC) and pancreatic cancer cells (Capan-1, MIAPaCa-2) were treated with the ceramide analogs (C2, AL6, C6 and C8), at low concentrations for 144h to evaluate any antiproliferative and pro-apoptotic effects, inhibition of migration, and to measure the expression of caveolin-1 (CAV-1) and thrombospondin-1 (TSP-1) mRNAs by real time RT-PCR. Assessment of ERK1/2 and Akt phosphorylation, and of CAV-1 and cyclin-D1 protein expression was performed by ELISA. Maximum tolerated dose (MTD) gemcitabine was compared against metronomic doses of the ceramide analogs by evaluating the inhibition of MIAPaCA-2 subcutaneous tumor growth in nude mice. Results. Metronomic ceramide analogs preferentially inhibited cell proliferation and enhanced apoptosis in endothelial cells. Low concentrations of AL6 and C2 caused a significant inhibition of HUVEC cell migration. ERK1/2 and Akt phosphorylation were significantly decreased after metronomic ceramide analog treatment. Such treatment caused the over-expression of CAV-1 and TSP-1 mRNA and protein in endothelial cells, whereas cyclin-D1 protein levels were reduced significantly. The antiangiogenic and antitumor impact in vivo of metronomic C2 and AL6 regimens was similar to that caused by MTD gemcitabine. C6 and C8 did not show any significant in vivo antitumor effects. Conclusions. Metronomic C2 and AL6 analogs have antitumor and antiangiogenic activity, determining the upregulation of CAV-1 and TSP-1 and the suppression of cyclin-D1

Decipher the glioblastoma microenvironment: The first milestone for new groundbreaking therapeutic strategies

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies

Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

e-Health solution for home patient telemonitoring in early post-acute TIA/Minor stroke during COVID-19 pandemic

Background: When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution. Objective: We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic. Methods: We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO2/temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event). Results: The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions. Conclusion: The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency

Whole-exome analysis in osteosarcoma to identify a personalized therapy

Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy. We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile