Hepatocellular carcinoma in two captive golden‐headed lion tamarins (Leontopithecus chrysomelas)

Two cases of hepatocellular carcinoma (HCC) in 2 female captive golden‐headed lion tamarins (Leontopithecus chrysomelas) are described. HCC was diagnosed in both, with pulmonary metastasis in one of them. Neoplastic cells were positive for hepatocyte‐specific antigen (HSA) by immunohistochemistry, confirming the diagnosis.     

Outcomes of endoscopic ultrasound‐guided pancreatic FNAC diagnosis for solid and cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme

Objective

To compare endoscopic ultrasound (EUS)‐FNAC diagnosis of pancreatic lesions with patient outcome based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme diagnostic categories: Panc 1 (non‐diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3 (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5 (suspicious of malignancy); and Panc 6 (positive/malignant).

Methods

All EUS‐FNA pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively classified according to the above scheme at the time of cytology reporting and data recorded prospectively. Subsequently, outcomes based on clinical follow‐up or histopathology diagnosis were compared with the cytology diagnosis.

Results

120 EUS‐FNA pancreas specimens from 111 patients were received, of which 112 (93.3%) specimens had follow‐up data. There were 79 and 41 EUS‐FNA pancreas specimens from solid and cystic lesions, respectively. Based on the cytology diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3 (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The performance indicators for diagnosis of malignancy or neoplasia with malignant potential, included sensitivity (95.4%), specificity (100%), positive predictive value (100%), negative predictive value (92.3%), false positive rate (0%) and false negative rate (4.6%).

Conclusions

The Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme is a logical system that can easily be introduced in a diagnostic cytopathology service. This classification scheme acts as an aid to diagnostic reporting, clear communication of significant results including risk of neoplasia/malignancy to clinicians, clinical audit and comparison of results with other centres.     

见微知著：微生物对人体恶性肿瘤诊疗研究带来的机遇与挑战

微生物与人体共生共存,主要分布在口腔、鼻腔、阴道、肠道、皮肤等部位,目前的研究已经表明微生物的分布特异性、种群的动态变化在人体恶性肿瘤的发生发展过程中发挥着重要的作用,为该领域今后的临床诊疗带来了全新的机遇和挑战。因此,笔者着重阐述微生物在口腔癌、胃癌、胆囊癌、胰腺癌、结直肠癌等常见恶性肿瘤中的作用及临床研究进展。旨在帮助临床医师了解目前微生物肿瘤学的发展现状及机遇与挑战。     

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP‐10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP‐9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP‐10 expression in UMSCC12 cells (p = 0.0001), and MMP‐3 (p = 0.0005) and ‐9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP‐2 (p = 0.0408) and MMP‐9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP‐2 (p = 0.0023) and ‐9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.     

Complications after breast reconstruction with alloplastic material in breast cancer patients submitted or not to post mastectomy radiotherapy

Background and purposeBreast reconstruction following mastectomy is a relevant element of breast cancer treatment. The purpose of this study was to evaluate the influence of radiotherapy (RT) on local complications in patients with breast cancer that had undergone breast reconstruction with alloplastic material.Materials and methodsRetrospective study of breast cancer patients submitted to mastectomy and breast reconstruction from 2009 to 2013. Clinical and treatment variables were correlated with early and late complications.Results251 patients were included; mean age was 49.7 (25 to 78) years. Reconstruction was immediate in 94% of the patients, with 88% performed with a temporary tissue expander. Postoperative radiotherapy (RT) was delivered to 167 patients (66.5%). Early complications were present in 26.3% of the patients. Irradiated patients presented 5.4% incidence of late complications versus 2.4% for non-irradiated patients (p = 0.327). Diabetes (OR = 3.41 95% CI: 1.23–9.45, p = 0.018) and high body mass index (BMI) (OR = 2.65; 95% CI: 1.60–4.37, p < 0.0001) were the main risk factors. The overall incidence of late complications was 4.4%, with predominance of severe capsular contracture (8/11). Arterial hypertension (OR = 4.78; 95% CI: 1.97–11.63, p = 0.001), BMI (OR = 0.170; 95% CI: 0.048–0.607, p = 0.006) and implant placement (OR = 3.55; 95% CI: 1.26–9.99, p = 0.016) were related to late complications.ConclusionsThe overall rate of complications was low in this population. Radiotherapy delivery translated into a higher but not statistically significant risk of late complications when compared with the non-irradiated patients. Already well-known clinical risk factors for complications after breast reconstruction were identified.     

Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha

An unbiased cDNA expression phage library derived from bone-marrow endothelial cells was used to identify novel surface adhesion molecules that might participate in metastasis. Herein we report that reticulocalbin 1 (RCN1) is a cell surface-associated protein on both endothelial (EC) and prostate cancer (PCa) cell lines. RCN1 is an H/KDEL protein with six EF-hand, calcium-binding motifs, found in the endoplasmic reticulum. Our data indicate that RCN1 also is expressed on the cell surface of several endothelial cell lines, including human dermal microvascular endothelial cells (HDMVECs), bone marrow endothelial cells (BMEC), and transformed human bone marrow endothelial cells (TrHBMEC). While RCN1 protein levels were highest in lysates from HDMVEC, this difference was not statistically significant compared BMEC and TrHBMEC. Given preferential adhesion of PCa to bone-marrow EC, these data suggest that RCN1 is unlikely to account for the preferential metastasis of PCa to bone. In addition, there was not a statistically significant difference in total RCN1 protein expression among the PCa cell lines. RCN1 also was expressed on the surface of several PCa cell lines, including those of the LNCaP human PCa progression model and the highly metastatic PC-3 cell line. Interestingly, RCN1 expression on the cell surface was upregulated by tumor necrosis factor alpha treatment of bone-marrow endothelial cells. Taken together, we show cell surface localization of RCN1 that has not been described previously for either PCa or BMEC and that the surface expression on BMEC is regulated by pro-inflammatory TNF-alpha.     

趋化因子配体18重组成熟肽段的表达

目的构建PET SUMO-CCL18原核表达质粒,并表达、纯化获得重组趋化因子配体18成熟肽段。方法从人卵巢癌组织中克隆CCL18基因全长,继而扩增表达成熟蛋白质的核酸序列,连接人PETSUMO载体,重组阳性克隆转入感受态细胞BL21（DE3）中IPTG诱导表达,基质辅助激光解吸／电离质谱技术（MALDI-TOF）验证后以SUMO蛋白酶切除载体部分,纯化浓缩,MALDI-TOF鉴定表达结果。结果测序分析证实,克隆人PETSUMO载体的CCL18序列与Genbank中报道序列完全一致,纯化后蛋白质谱鉴定与天然CCL18成熟蛋白序列一致。结论成功构建了高表达CCL18蛋白的表达系统,得到重组CCL18成熟肽段,为进一步研究CCL18蛋白在卵巢癌中的作用提供实验基础。     

表达人乳头瘤病毒16型E6/E7融合蛋白的非复制型重组痘苗病毒的构建及免疫效果观察

采用基因工程方法将HPV16E6、E7基因融合后插入痘苗病毒载体,通过同源重组构建表达人乳头瘤病毒16型E6/E7融合蛋白的非复制型重组痘苗病毒疫苗,用C57BL/6小鼠观察其免疫原性和抗肿瘤移植情况。测序结果表明融合的HPV16E6、E7基因序列与设计相符;构建的非复制型重组痘苗病毒经Dot blot鉴定,显示有E6、E7融合基因的插入;Western blot检测表明该重组病毒在鸡胚成纤维细胞中能表达HPV16型E6/E7融合蛋白。动物免疫试验表明,该重组病毒在小鼠体内可诱发E6、E7特异性抗体;被免疫小鼠能抵抗TC-1肿瘤细胞的攻击。此结果为将来进一步研制HPV16、18型联合疫苗打下了基础。     

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma

Pancreatic adenosquamous carcinoma (PASC) — a rare pathological pancreatic cancer (PC) type — has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.     

A case of maxillary sarcoma in a chimpanzee (Pan troglodytes)

Oral malignancy is rare in chimpanzees. A 34‐year‐old female chimpanzee (Pan troglodytes) at Kumamoto Sanctuary, Japan, had developed it. Treatment is technically difficult for chimpanzees while malignant neoplasm is seemingly rising in captive populations. Widespread expert discussion, guidelines for treatment, especially for great apes in terminal stages is urgently needed.