Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review.

Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.

Lipid-based nanosystems: the next generation of cancer immune therapy.

Immunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical use thereof. These limitations are partially alleviated by delivery systems. Lipid-based nanoparticles (NPs) have emerged as revolutionary carriers due to favorable physicochemical characteristics, with specific applications and strengths particularly useful in immunotherapeutic agent delivery. The aim of this review is to highlight the challenges faced by immunotherapy and how lipid-based NPs have been, and may be further utilized to address such challenges. We discuss recent fundamental and clinical applications of NPs in a range of areas and provide a detailed discussion of the main obstacles in immune checkpoint inhibition therapies, adoptive cellular therapies, and cytokine therapies. We highlight how lipid-based nanosystems could address these through either delivery, direct modulation of the immune system, or targeting of the immunosuppressive tumor microenvironment. We explore advanced and emerging liposomal and lipid nanoparticle (LNP) systems for nucleic acid delivery, intrinsic and extrinsic stimulus-responsive formulations, and biomimetic lipid-based nanosystems in immunotherapy. Finally, we discuss the key challenges relating to the clinical use of lipid-based NP immunotherapies, suggesting future research directions for the near term to realize the potential of these innovative lipid-based nanosystems, as they become the crucial steppingstone towards the necessary enhancement of the efficacy of immunotherapy.

Erratum: Acute cellular and vascular responses to photodynamic therapy using EGFR-targeted nanobody-photosensitizer conjugates studied with intravital optical imaging and magnetic resonance imaging: Erratum.

[This corrects the article DOI: 10.7150/thno.37949.].

Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

OBJETIVO: Avaliar o potencial benéfico da histamina combinada ao melfalano, na perfusão de membro isolado (PMI), como alternativa à combinacão TNF-alfa mais melfalano, no tratamento de sarcomas de partes moles irressecaveis em extremidades, em ratos de linhagem Brown Norway (BN). MÉTODOS: 20 ratos BN foram submetidos a implantacão de fragmentos de fibrosarcoma singênico BN-175 na pata traseira direita. Em cerca de 7-10 dias o tumor atingiu um diâmetro médio de 12-15 mm e foram aleatóriamente divididos em quatro grupos (controle, melfalano,histamina em doses progessivas combinada ao melfalano e histamina) sendo submetidos a PMI experimental por 30 minutos. Os tumores foram então medidos diariamente com o uso de paquímetro e o volume tumoral calculado. RESULTADOS: As curvas de resposta mostram um efeito significativo da combinacão de Histamina na concentracão de 200 mg/mL ao melfalano, com 66% de resposta global incluindo 33% de respostas completas (p < 0.01). Não houve efeitos colaterais sistêmicos e localmente apenas edema leve e transitório nos animais tratados com histamine. CONCLUSAO: A histamina em combinacão com o melfalano apresenta um efeito promissor na PMI garantindo maiores investigacões do seu mecanismo de acão e do seu potencial uso na perfusão de órgãos.