Antineoplastic impact of leishmanial sphingolipid in tumour growth with regulation of angiogenic event and inflammatory response
Abstract Very often conventional therapy, i.e. chemotherapeutic treatment, develops resistance in cancer cells and fails to be effective against disease states. An alternative strategy or a new entity may resolve the problem. Interestingly, the microbial world has begun to be explored in medicinal research as a potential new source to deliver bio-active molecules such as sphingolipids for efficacious cancer treatment. A sphingolipid of microbial origin, especially from Leishmania donovani (LSPL), is a novel entity which may exert anti-cancer activity by regulating cellular growth. The present study reveals that among a range of cancer cells evaluated, LSPL-1 (a component of LSPL) reduces cell viability, annexin exposures and arrests cell cycle in B16F10 cells in a concentration and time dependent manner. Flowcytometric analysis showed that it alters mitochondrial membrane potential and generates a number of ROS positive melanoma cells. It activates p53 at serine anchor region via up-regulation of p21 subunit along with PUMA and NOXA. It also exerts activity in vivo by reducing tumor micro vessel and mitotic index while simultaneously improving the survival rate. The inflammatory responses including elevated level of cytokine-chemokine and increased expression of PCNA and F480 are subdued by LSPL-1 treatment in tumour bearing mice. Besides, it reduces the metastatic outburst of angiogenic factors like VEGF, Ang-2, and CD34 through the involvement of several growth pr...
Authors: Bilkhu R, Billè A Abstract The coronavirus 2019 (COVID-19) pandemic has caused significant mortality around the world and the focus has been on reducing the number of infections. In order not to compromise treatment of oncology patients, reducing the number of patients with COVID-19 undergoing treatment is mandatory. We reviewed the experience of the National Institute of Cancer in Milan and compared it with our experience. PMID: 32462984 [PubMed - as supplied by publisher]
Conclusion: Adding a BM-TT to FIT-screening considerably reduces colonoscopy burden, but could also decrease screening effectiveness. Combining FIT15 with a high polyp sensitivity BM-TT seems most promising. PMID: 32462913 [PubMed - as supplied by publisher]
SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA
This issue of the Surgical Oncology Clinics of North America is devoted to covering the important topic of melanoma. The incidence of primary cutaneous melanoma continues to increase each year. While melanoma accounts for the majority of skin cancer –related deaths, surgical treatment of early disease can be curative. Over the last decade, there have been marked changes in the surgical and systemic treatment of melanoma. For example, within the surgical field, there have been multiple prospective randomized clinical trials to define the exten t of surgery with important changes to how the nodal basin should be managed and staged.
The management of melanoma has undergone a radical transformation over the past decade. Beginning with the publication of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) in 2006 and most recently with the results of the MSLT-2 trial in 2017, the surgical management of patients with this disease has evolved at a remarkable pace. In addition, substantial improvements in systemic therapy have prompted an exploration of neoadjuvant approaches, combination therapy, and many other attractive therapeutic endeavors.
With the universal adoption of immune checkpoint blockade and agents targeting BRAF-mutated melanomas in the metastatic setting, numerous clinical trials have evaluated these agents in the neoadjuvant setting. These smaller trials have shown promising results with high pathologic response rates and acceptable safety. Larger prospective randomized trials are under way to determine if all patients with resectable metastatic disease should be receiving neoadjuvant therapy.
We describe lesions ranging from the potentially benign to the likely malignant. Correctly identifying features associated with higher-risk lesions has proven challenging given the overall good prognosis and low rate of events. An appropriate treatment plan generally requires discussion between the surgeon and an experienced dermatopathologist. When clinically indicated, additional testing may be used to further support or refute a diagnosis of melanoma. The indications for these techniques, the data to support their use, and the strengths and weakness of each are reviewed.
Clinical outcomes for metastatic melanoma have been dramatically altered by recent developments in immunotherapy and targeted strategies, but response to these therapies is not uniform, the majority of patients do not respond, and clinical response can be self-limited. Current directions in melanoma treatment aim to leverage a combination of therapies for tumors refractory to monoimmunotherapy, to include tumor-directed strategies, such as intralesional therapy and inhibitors designed for novel targets, which may augment current systemic agents when used in combination. Here, we summarize new classes of agents and emerging...
Stage IV melanoma has a 5-year survival rate of 6%, but considerable advances have been made in systemic therapies. Systemic immunotherapy has achieved durable responses in up to 40% of patients, with similar improvements with targeted therapies. This has reshaped the landscape for surgery in stage IV melanoma. Metastasectomy can be considered in patients on systemic immunotherapy or targeted therapy with responding, stable, or isolated progressing lesions, oligometastatic disease, or long disease-free intervals. Surgery plays a role in providing tumor tissue for preparation of tumor-infiltrating lymphocytes for adoptive c...
This article presents the current data supporting adjuvant therapy for patients with cutaneous melanoma. With the recent development of novel immunotherapy agents as well as targeted therapy, there are strong data to support the use of these therapies in patients at high risk of developing recurrent or metastatic disease.