Colorectal cancer is one of the most frequent cancers worldwide, having the fourth mortality rate among cancers in both sexes. Numerous studies are investigating the signalling pathways and different factors involved in the development and progression of colorectal cancer. It has recently been shown that the S-phase kinase-associated protein 2 (Skp2) overexpression plays an important role in the pathogenesis of colorectal cancer. We review the role of Skp2 and its ubiquitin-proteasome pathway in colorectal cancer. The F-box protein Skp2, a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex, has been shown to regulate cellular proliferation, cancer progression and metastasis by targeting several cell cycle regulators for ubiquitination and subsequent 26S proteasome degradation. The best known protein substrate of the Skp2 is the cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27Kip1. Overexpression of Skp2 and loss of CDKN1B (p27) was strongly associated with aggressive tumor behavior and poor clinical outcome in a variety of cancers, including colorectal cancer. An efficient interaction between Skp2 and CDKN1B (p27) requires the presence of an essential activator of the SCF-Skp2 complex, the cyclin-dependent kinase subunit 1 (Cks1) cofactor. Alterations in the Skp2, Cks1 and CDKN1B (p27) expression have major effects on colorectal carcinogenesis and may serve as an important and independent prognostic marker. Furthermore, we highlight that Skp2 may be a promising therapeutic target for colorectal cancer, and development of Skp2 inhibitors would have a great impact on colorectal cancer therapy.
PURPOSE The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care. METHODS We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes. RESULTS Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care. CONCLUSION This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.
A normal evolution of the cell-cycle phases consists of multiple consecutive events, which makes it a highly complex process. Its preservation is regulated by Cyclin-Cdks (cyclin-dependent kinases) interactions and protein degradation, which is often controlled by the ubiquitin-mediated proteolysis.The goal of this review is to emphasize the most important features of the regulation of the cell-cycle involved in cancerogenesis, by presenting the involvement of E3 ubiquitin ligases SCF (Skp1-Cul1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome) in human malignancies. Also, we discuss the importance of the ubiquitin proteasome pathway blockade in cancer treatment. We know that a better understanding of the regulatory biology of the cell cycle can lead to the development of new target therapies for cancer.
Background and aimSolid pseudopapillary tumor (SPT) of the pancreas is a rare pathological condition, representing less than 3% of all exocrine pancreatic tumors. SPT usually occurs in young females, without notable symptoms, with a low malignant potential and excellent prognosis.MethodWe conducted a retrospective study during the period January 2005 – January 2015. SPT patients admitted in our institution were reviewed by describing demographic data, clinico-pathologic and radiological features, therapeutic management and prognosis records.ResultsThirteen patients with SPT were identified (10 females), with a median age of 30 years. The main clinical presentation was abdominal pain (92.3%). The tumor was mostly located in the body or tail of the pancreas (77%), and the mean size was 8.2 cm. Regarding the surgical approach there were 5 distal pancreatectomies with splenectomy, 3 body and tail pancreatectomies, 2 body and tail pancreatectomies with splenectomy, 2 pancreato-duodenectomy, 1 partial enucleation and of all only 2 partial resections. Postoperative hematoxylin- eosin staining and immunohistochemistry confirmed the diagnosis in all cases. None of the patients had lymph nodes metastases. Only one local invasion. There was one case of death due to postoperative complications. Four cases followed adjuvant systemic chemotherapy. The mean follow-up was 18 months, without evidence of recurrence during this period.ConclusionSPT should always be considered in the differential diagnosis in young women with a pancreatic tumor. Complete surgical excision is the treatment of choice, and is usually curative. The decision to administer systemic therapy must be individualized. Malignant behavior and late recurrences mandates long-term follow-up for patients with SPT.
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