抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

/pdf/tumour-exosome-integrins-determine-organotropic-metastasis-379nlmfm16.pdf

Tumour exosome integrins determine organotropic metastasis

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.

/pdf/tumour-evolution-inferred-by-single-cell-sequencing-2d93wjd7r9.pdf

Tumour evolution inferred by single-cell sequencing

Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results.

Human Papillomavirus and Cervical Cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online) 

Identification of adrenocortical masses malignancy and aggressivity through radiomics: a pilot study

Liquid biopsy (LB) is an emerging diagnostic tool that analyzes biomarkers in the blood (and possibly in other body fluids) to provide information about tumor genetics and response to therapy. This review article provides an overview of LB applications in human cancer with a focus on breast cancer patients. LB methods include circulating tumor cells and cell-free tumor products, such as circulating tumor DNA. LB has shown potential in detecting cancer at an early stage, monitoring tumor progression and recurrence, and predicting patient response to therapy. Several studies have demonstrated its clinical utility in breast cancer patients. However, there are limitations to LB, including the lack of standardized assays and the need for further validation. Future potential applications of LB include identifying the minimal residual disease, early detection of recurrence, and monitoring treatment response in various cancer types. LB represents a promising non-invasive diagnostic tool with potential applications in breast cancer diagnosis, treatment, and management. Further research is necessary to fully understand its clinical utility and overcome its current limitations.

/pdf/liquid-biopsy-in-the-management-of-breast-cancer-patients-2svhltwv.pdf

Liquid Biopsy in the Management of Breast Cancer Patients: Where Are We Now and Where Are We Going

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006-2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006-2010); period B (2011-2015) and period C (2016-2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P < 0.001) showed significant differences. Computed tomography scans (P < 0.001), endoscopic ultrasound (P < 0.001), fine needle aspiration, fine needle biopsy (P < 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P < 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P < 0.001). The MDTB evaluation increased significantly (P < 0.001). Up-front surgery and exploratory laparotomy decreased (P < 0.001), neoadjuvant treatment increased (P < 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential. 

/pdf/evolving-knowledge-in-surgical-oncology-of-pancreatic-cancer-hxixlu7d.pdf

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice—a fifteen-year journey at a tertiary referral centre

1 Misciali C, Iorizzo M, Fanti PA et al. Onychoblastoma (hamartoma of the nail unit): a new entity? Br J Dermatol 2005; 152:1077–8. 2 Baran R, Kint A. Onychomatrixoma. Filamentous tufted tumour in the matrix of a funnel-shaped nail: a new entity (report of three cases). Br J Dermatol 1992; 126:510–15. 3 Perrin C, Goettmann S, Baran R. Onychomatricoma. Clinical and histopathologic findings in 12 cases. J Am Acad Dermatol 1998; 39:560–4. 4 Pommepuy I, Roblet D, Blaise S et al. Onychomatricoma, a rare lesion of the nail. Ann Pathol 2004; 24:368–70. 5 Kint A, Baran R, Geerts ML. The onychomatricoma: an electron microsopic study. J Cutan Pathol 1997; 24:183–8. 6 Perrin C, Baran R, Pisani A et al. The onychomatricoma—additional histologic criteria and immunohistochemical study. Am J Dermatopathol 2002; 24:199–203.

Is onychoblastoma really a new entity?: reply from authors

Case Report Phyllodes tumor continue to provide diagnostic and therapeutic dilemmas particularly in young age. We report a rare case of phyllodes tumor of the breast (cystic-papillary variant) of a 10 years old female with bloodymonolateral nipple discharge. Only another case of giant benign phyllodes tumor in a juvenile patient with bloody nipple discharge is published in literature, but this case report deals about the youngest patient in literature.

/pdf/a-pediatric-giant-phyllodes-tumor-and-bloody-nipple-vhh7wqj8d7.pdf

Donatella Santini

Papers

Identification of adrenocortical masses malignancy and aggressivity through radiomics: a pilot study

Liquid Biopsy in the Management of Breast Cancer Patients: Where Are We Now and Where Are We Going

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice—a fifteen-year journey at a tertiary referral centre

Is onychoblastoma really a new entity?: reply from authors

A Pediatric Giant Phyllodes Tumor and Bloody Nipple Discharge: A Rare Case Report