Association of tumor budding with tumor-infiltrating lymphocytes and prognosis in breast cancer patients

AIM: To investigate the relationship of tumor budding with clinicopathologic parameters, tumor-infiltrating lymphocytes (TILs) of tumor microenvironment and the prognosis in breast cancer patients.METHODS: A total of 178 HE section samples were collected from the breast cancer patients treated with surgery in the First Affilated Hospital of Jinan University during Jan. 2012 to Dec. 2016. The tumor budding and stromal tumor-infiltrating lymphocytes were observed under light microscope. The correlation of tumor budding with the clinicopathologic status and TILs were analyzed by χ² test. Kaplan-Meier survival analysis and Log-rank test were used to estimate the disease-free survival (DFS) and overall survival (OS).RESULTS: High tumor budding level was associated with more positive lymph nodes, higher grade, and more lymphovascular invasion. In addition, the patients with higher tumor budding level showed fewer TILs, while the patients with lower tumor budding level had more TILs. Furthermore, the patients with higher tumor budding level had a worse disease-free survival and overall survival than those with lower tumor budding level.CONCLUSION: Tumor budding is significantly associated with adverse clinicopathological characteristics of breast cancer and negatively correlated with TILs. Therefore, tumor budding may serve as a potential biomarker to predict the prognosis of breast cancer.     

Inhibition of telomerase in canine cancer cells following telomestatin treatment

Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.     

Expression of miRNA-22 in ovarian cancer and effect of miRNA-22 over-expression on SKOV-3 ovarian cancer cell proliferation,migration and invasion

AIM: To examine the expression of miRNA-22 in the ovarian tissues and the effect of miRNA-22 over-expression on the proliferation, migration and invasion in SKOV-3 cells. METHODS: The expression levels of miRNA-22 in different ovarian tissues and SKOV-3 cells were determined by qPCR. miRNA-22 was over-expressed by transfection of miRNA-22 mimic. The cell viability was examined by CCK-8 assay. The cell migration was measured by wound healing test. The cell invasion was analyzed by Transwell assay. The protein expression levels of VEGF and P53 were determined by Western blot. RESULTS: Compared with the normal ovarian tissue, the expression level of miRNA-22 was remarkably decreased in the ovarian tumor tissues. After transfection with miRNA-22 mimic, the expression level of miRNA-22 in the SKOV-3 cells was significantly increased, while the cell viability, migration and invasion were obviously decreased. Moreover, the protein expression of VEGF and P53 was dramatically inhibited after over-expression of miRNA-22. CONCLUSION: The decreased miRNA-22 expression may be correlated with the development of ovarian can-cer. Over-expression of miRNA-22 decreases the cell viability, migration and invasion by reducing the protein expression of VEGF and P53.     

Juglone inhibits epithelial-mesenchymal transition of prostate cancer cells by regulating Wnt/β-catenin/Snail signaling pathway

AIM: To investigate the mechanism of juglone on epithelial-mesenchymal transition in prostate cancer cells. METHODS: Human prostate cancer LNCaP cells were divided into control group (without juglone), 12.5 μmol/L juglone group and 25 μmol/L juglone group. LNCaP cells in the latter 2 groups were treated with juglone for 24 h. The invasion ability of the LNCaP cells was detected by Transwell assay. The protein expression of E-cadherin, vimentin, Snail and β-catenin was determined by Western blot. The LNCaP cells were treated with LiCl and juglone in combination for 24 h, and the protein expression of Snail and E-cadherin was detected by Western blot.RESULTS: The results of Trans-well invasion assay showed that the invasion ability in juglone groups was significantly decreased (P<0.01). The protein expression of E-cadherin in the LNCaP cells treated with juglone was increased, and the expression levels of vimentin and β-catenin were reduced (P<0.01). Treatment with LiCl significantly attenuated the inhibitory effect of juglone on Snail expression and subsequent down-regulation of E-cadherin expression. CONCLUSION: Juglone inhibits the epithelial-mesenchymal transition by inhibiting the Wnt/β-catenin/Snail signaling pathway in the LNCaP cells.     

云南松松塔提取物对H22实体瘤小鼠模型的抑瘤作用

研究云南松松塔乙醇提取物(PEA)和碱水提取醇沉物(PED)对H22实体瘤小鼠的抑瘤作用。建立H22实体瘤小鼠模型,随机分组,灌胃给药,1次/d,给药10d。末次给药24h后,取血检测γ干扰素(IFN-γ)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)含量;剥离肿瘤组织并称重,计算抑瘤率;检测肿瘤组织匀浆中环氧化酶-2(COX-2)和前列腺素E2(PGE2)含量;石蜡包埋HE染色观察肿瘤细胞病理组织学变化。结果显示,PEA和PED各剂量组小鼠平均肿瘤重量较模型组显著减小;最大抑瘤率分别达46.11%和58.05%。PEA和PED各剂量组小鼠外周血中IFN-γ和IL-2含量较模型组显著升高;IL-4和IL-10含量较模型组显著降低。PEA和PED各剂量组小鼠肿瘤组织中COX-2和PGE2含量较模型组显著减少;给药组正常肿瘤组织减少,有出血和坏死,脂肪组织增多。结果表明,PEA和PED可抑制H22实体瘤小鼠的肿瘤生长,其机制与调节Th1/Th2细胞平衡和抑制COX-2与PGE2的表达有关。     

A novel MCT1 and MCT4 dual inhibitor reduces mitochondrial metabolism and inhibits tumour growth of feline oral squamous cell carcinoma

Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC.     

ULTRASONOGRAPHIC FEATURES OF PARAPROSTATIC CYSTS IN NINE DOGS

The ultrasonographic features of paraprostatic cysts in nine dogs are described along with historical, clinical, surgical and pathologic findings. Cysts occurred predominantly in older, large breed dogs (mean age 8 years, range 3–11 years). The most common presenting complaints were depression, inappetance, stranguria, tenesmus and bloody penile discharge. A palpable abdominal mass was the most common physical finding. Ultrasonographically, paraprostatic cysts were usually large anechoic structures; many contained internal septa. Moderately large anechoic cavities or cysts were also detected in the prostatic parenchyma of five dogs, and in two of these communication with the paraprostatic cyst was visualized. There were no clearly distinct ultrasonographic criteria to discriminate septic from nonseptic paraprostatic cysts.     

Comparison of first-opinion and second-opinion histopathology from dogs and cats with cancer: 430 cases (2001–2008)

Second-opinion histopathology is intended to detect clinically significant discrepancies that have a direct impact on patient care. We sought to determine if this practice at our institution affected patient management and prognosis. First- and second-opinion histopathology reports from cases were retrospectively reviewed. Reports were considered to be in diagnostic agreement, partial diagnostic disagreement or complete diagnostic disagreement. Four hundred and thirty cases were studied. In 70% of cases there was a diagnostic agreement. In 20% of cases, there was partial diagnostic disagreement, where diagnoses were the same but information such as grade or lymphatic and/or vascular invasion was changed. In 10% of cases, complete diagnostic disagreement resulted from a change in degree of malignancy (malignant to benign, or converse; 7%) or a change in cell type (3%). In 17% of the cases evaluated, the histopathology review prompted a change in treatment or prognosis. These findings support the use of second-opinion histopathology as an important part of patient care.     

犬前列腺疾病概述

犬前列腺疾病是临床常见的公犬泌尿生殖道疾病,通常发生于老龄公犬,特别是6岁以上的未去势公犬。常见的犬前列腺疾病主要有前列腺炎、良性前列腺增生、前列腺囊肿、前列腺脓肿和前列腺癌。前列腺疾病的临床表现相似,表现为排尿困难、尿淋漓、血尿、前列腺液成分改变、便秘等,因此仅从病史、临床症状方面难以对疾病进行确诊,需要借助于X光检查、B超检查、前列腺液检查、组织/细胞学检查等特殊的诊断方法。在确诊的基础上根据不同的发病原因采取抗生素治疗,去势,前列腺切除手术等治疗方法。论文对各种常见犬前列腺疾病的病因、临床表现、诊断和治疗方案进行综述。