Circulating Biomarkers for Tumor Angiogenesis: Where Are We?

BACKGROUND: In recent years, several anti-angiogenic drugs have been developed and their addition to standard treatment has been associated with clinical benefits. However, the response to anti-angiogenic therapy is characterized by considerable variability. In this context, the development of dynamic non-invasive biomarkers would be helpful to elucidate the emergence of anti-angiogenic resistance as well as to correctly address the treatment. OBJECTIVES: The purpose of this review is to describe current reports on circulating diagnostic and prognostic biomarkers related to angiogenesis. We further discuss how this non-invasive strategy could improve the monitoring of tumor treatment and help clinical strategy. RESULTS: We discuss the latest evidence in the literature regarding circulating anti-angiogenic markers. Besides growth factor proteins, different circulating miRNAs could exert a pro- or anti-angiogenic activity so as to represent suitable candidates for a non-invasive strategy. Recent reports indicate that tumor-derived exosomes, which are small membrane vesicles abundant in biological fluids, also have an impact on vascular remodeling. CONCLUSION: Numerous circulating biomarkers related to angiogenesis have been recently identified. Their use will allow identifying patients who are more likely to benefit from a specific anti-angiogenic treatment, as well as detecting those who will develop resistance and/or adverse effects. Nonetheless, further studies are required to elucidate the role of these biomarkers in clinical settings.

Acute Lymphoblastic Leukemia with Hypereosinophilia in a Child: Case Report and Literature Review.

Background: Hypereosinophilia in children can be primary or secondary. Numerous malignant diseases can cause hypereosinophilia, but it is seldom caused by acute lymphoblastic leukemia (ALL). In the event of protracted hypereosinophilia, it is extremely important to make a correct differential diagnosis. Case presentation: We present the case of an 11-year-old boy of Moroccan origin with ALL with hypereosinophilic onset (eosinophils in peripheral blood, 10,000/µL) in the absence of other signs of neoplastic disease, and compare this case with 61 similar cases in the literature. Following hospital admission, the patient initially presented with headache-caused nocturnal awakenings, evening fever, and cough, and he also lost approximately 7 kg in weight in a month not associated with sweating or itching. We first performed bone marrow aspiration, which showed an increase in eosinophils without cellular morphological abnormalities, and bone marrow immunophenotyping showed that 4.5% of cells had a phenotype compatible with lymphoid blasts. A lumbar puncture was negative. Given the poor marrow involvement, it was necessary to repeat a new bone marrow aspiration two days later, which showed an increase in blasts to 14%. A concomitant bone marrow biopsy showed an infiltration of blasts typical of B-cell ALL equal to 20⁻30% with associated hypereosinophilia. Cytogenetic analysis showed an hyperdiploid karyotype: 53⁻55, XY, +X, add(1)(q21q25), +4, +9, +10, +14, +2, +1, +21/46, XY. Conclusions: ALL is one of the possible causes of persistent hypereosinophilia. In patients with ALL and hypereosinophilia, peripheral hypereosinophilia can precede the appearance of blasts. Due to the negative prognosis and the increased risk of complications in these patients, bone marrow aspiration and biopsy are recommended if common causes of secondary hypereosinophilia are excluded.

Intraspinal mesenchymal chondrosarcoma: report of a pediatric case and literature review.

PURPOSE: Mesenchymal chondrosarcoma (MCS) is an aggressive variant of chondrosarcoma and is a rare tumor, particularly within the pediatric population. Commonly, MCS originates in the bone, but it can also arise in extraskeletal sites, such as the brain and the intraspinal area. Due to the rarity of this tumor, there are no guidelines for its optimal treatment. METHODS: We report a case of intradural extramedullary MCS, located at the T11-T12 level, in a 14-year-old male. The tumor was documented by magnetic resonance imaging and treated with gross total resection (GTR) without adjuvant treatment. We further reviewed the relevant pediatric literature and discussed the management and outcome of intracranial and intraspinal MCS. RESULTS: The patient's follow-up showed no evidence of disease 2 years from diagnosis. A total of 51 cases of intracranial and intraspinal MCS have been reported (24 intraspinal and 27 intracranial). Recurrence has been described in only 4 patients with intraspinal MSC, and among them 3 received adjuvant chemotherapy and radiotherapy. GTR seems to reduce the risk of recurrence and, due to a higher cancer-mortality rate for these patients, adjuvant chemotherapy and radiotherapy are recommended in case aggressive surgery is not possible. CONCLUSIONS: According to our single experience, we would suggest that adjuvant therapy might be unnecessary in cases where a localized MCS undergoes GTR. Chemotherapy and radiotherapy should be recommended when GTR cannot be obtained. Further studies are needed to investigate a standard treatment approach for this rare tumor.