Cancer-on-chip: a 3D model for the study of the tumor microenvironment.

The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans.

Clinical recommendations for diagnosis and treatment according to current updated knowledge on BIA-ALCL.

Shared strategies and correct information are essential to guide physicians in the management of such an uncommon disease as Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). A systematic review of the literature was performed to collect the most relevant evidence on BIA-ALCL reported cases. A panel of multidisciplinary experts discussed the scientific evidence on BIA-ALCL, and updated consensus recommendations were developed through the Delphi process. The lastest reported Italian incidence of BIA-ALCL is 3.5 per 100.000 implanted patients (95% CI, 1.36 to 5.78), and the disease counts over 1216 cases worldwide as of June 2022. The most common presentation symptom is a late onset seroma followed by a palpable breast mass. In the event of a suspicious case, ultrasound-guided fine-needle aspiration should be the first step in evaluation, followed by cytologic and immunohistochemical examination. In patients with confirmed diagnosis of BIA-ALCL confined to the capsule, the en-bloc capsulectomy should be performed, followed by immediate autologous reconstruction, while delayed reconstruction applies for disseminate disease or radically unresectable tumor. Nevertheless, a multidisciplinary team approach is essential for the correct management of this pathology.

Spiked Helmet Electrocardiographic Sign in a Patient with a Diagnosis of Thoracoabdominal Aortic Dissection.

We report the case of a patient who developed the spiked helmet electrocardiographic (ECG) sign concomitantly with a thoracoabdominal aortic dissection resulting in ischemic functional ileum with gastric distention. Prompt identification of this ECG sign could prevent unnecessary emergent percutaneous cardiac catheterization procedures. (Level of Difficulty: Beginner.).

Predation of the Buffy-fronted Seedeater Sporophila frontalis (Aves: Emberizidae) on Merostachys neesii (Poaceae: Babusoideae) seeds during a masting event in the Atlantic forest / Predação do pixoxó Sporophila frontalis (Aves: Emberizidae) em sementes de Merostachys neesii (Poaceae: Babusoideae) durante um evento de frutificação em massa na floresta Atlântica

The Buffy-fronted Seedeater Sporophila frontalis (Verreaux, 1869) is frequently found foraging on seeds during ephemeral masting events of bamboos in the Atlantic forest. In the present study, we analyzed the predation activity of S. frontalis on seeds of Merostachys neesii Rupr. during a masting event in an Atlantic forest reserve on southeastern Brazil. We conducted point counts in spots with M. neesii and in spots without bamboos along trails to determine the presence of S. frontalis on M. neesii clumps. Additionally, focal observations on bamboo clumps and seed traps were used to verify the predatory impact of S. frontalis on M. neesii seeds. S. frontalis was present in 6 out 18 point counts in M. neesii clumps. The seedeater behaved territorially in bamboo clumps and presented a mean predation rate of 1.10 bamboo seeds/minute. Seed traps had up to 80 percent of the seeds predated. The large amount of seeds available during bamboo masting events probably contributes to the maintenance of wandering populations of S. frontalis in the Atlantic forest. On the other hand, the predation of seeds by S. frontalis may reduce the reproductive germination and the propagation of the bamboos whose growth may in turn negatively affect the establishment of other forest species.

O pixoxó Sporophila frontalis (Verreaux, 1869) é freqüentemente encontrado forrageando em sementes durante eventos de frutificação em massa de bambus na floresta Atlântica. No presente estudo, nós analisamos a atividade de predação de S. frontalis em sementes de Merostachys neesii Rupr. durante um evento de frutificação em uma reserva da floresta Atlântica no sudeste do Brasil. Nós conduzimos pontos de contagem em locais com M. neesii e em locais sem bambus ao longo de trilhas para determinar a presença de S. frontalis em touceiras de M. neesii. Adicionalmente, observações focais e coletores de sementes foram utilizados em touceiras de M. neesii para verificar o impacto de predação em sementes realizado pelo pássaro. Sporophila frontalis esteve presente em 6 de 18 pontos de contagem com touceiras de M. neesii. Esta espécie se comportou territorialmente em touceiras de bambu e apresentou uma taxa de predação média de 1.10 sementes/minuto. Os coletores de sementes possuíram até 80 por cento das sementes predadas. Provavelmente, a enorme quantidade de sementes disponíveis durante eventos de frutificação em massa de bambus contribuem para a manutenção de populações vagantes de S. frontalis na floresta Atlântica. Por outro lado, a predação de sementes por S. frontalis pode reduzir a germinação reprodutiva e a propagação de bambus, cujo crescimento interfere negativamente no estabelecimento de outras espécies de plantas arbóreas.

Hematology and serum chemistry parameters in juvenile cynomolgus monkeys (Macaca fascicularis) of Mauritius origin: comparison between purpose-bred and captured animals.

BACKGROUND: The vast majority of non-human primates used for experimental activities are purpose-bred. However, in case of particular procedures or specific projects, it may still be necessary to use animals captured in the wild. METHODS: Sixty cynomolgus monkeys were randomly selected on the basis of breeding origin, and assigned to two groups, each of fifteen males and fifteen females. Analyses included the most frequently investigated parameters for hematology, coagulation, and biochemistry. RESULTS: Differences were observed in some parameters, particularly in eosinophils, basophils and monocytes, and in fibrinogen, total protein, globulins, alanine amino-transferase, creatinine, aspartate amino-transferase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, iron, potassium, and phosphorus. CONCLUSIONS: Some values in the cynomolgus monkey may show significant differences according to the breeding background of the animals. Only data obtained from animals of similar origin have to be compared, to avoid misinterpretation during the evaluation of the experimental results.

Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients.

PURPOSE: To investigate the activity of letrozole plus/minus oral metronomic cyclophosphamide as primary systemic treatment (PST) in elderly breast cancer patients. METHODS: One hundred fourteen consecutive elderly women with T2-4 N0-1 and estrogen receptor-positive breast cancer were randomly assigned to primary letrozole therapy (2.5 mg daily for 6 months) or a combination of letrozole plus oral cyclophosphamide (50 mg/daily for 6 months) in an open-labeled, randomized phase II trial. Tumor response was assessed clinically, and tumor Ki67 index and vascular endothelial growth factor (VEGF) -A levels were measured before and after treatment. RESULTS: Overall response rate was 71.9% (95% CI, 60.0 to 83.8) in the 57 patients randomly assigned to receive primary letrozole and 87.7% (95% CI, 78.6 to 96.2) in the 57 patients randomly assigned to receive letrozole plus cyclophosphamide. The difference in activity between treatment arms was predominantly confined to patients with ductal histology. There was a significantly greater suppression of Ki67 and VEGF-A expression in the letrozole/cyclophosphamide-treated group than in the letrozole-treated group, leading to lower Ki67 and VEGF expression at post-treatment residual histology (P = .03 and P = .002, respectively). CONCLUSION: Both letrozole and letrozole plus cyclophosphamide treatments appeared active as PST in elderly breast cancer patients. Metronomic scheduling of cyclophosphamide may have an antiangiogenic effect and the combination of letrozole plus cyclophosphamide warrants testing in a randomized phase III trial.