Invasion Of Surrounding Tissues Research Articles

Imaging characteristics and diagnosis of primary middle mediastinal tumors

Objectives: To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Methods: Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. Results: The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Conclusion: Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.

The Role of miRNAs to Detect Progression, Stratify, and Predict Relevant Clinical Outcomes in Bladder Cancer.

Bladder cancer (BC) is one of the most common types of cancer worldwide, with significant differences in survival depending on the degree of muscle and surrounding tissue invasion. For this reason, the timely detection and monitoring of the disease are important. Surveillance cystoscopy is an invasive, costly, and uncomfortable procedure to monitor BC, raising the need for new, less invasive alternatives. In this scenario, microRNAs (miRNAs) represent attractive prognostic tools given their role as gene regulators in different biological processes, tissue expression, and their ease of evaluation in liquid samples. In cancer, miRNA expression is dynamically modified depending on the tumor type and cancer staging, making them potential biomarkers. This review describes the most recent studies in the last five years exploring the utility of miRNA-based strategies to monitor progression, stratify, and predict relevant clinical outcomes of bladder cancer. Several studies have shown that multimarker miRNA models can better predict overall survival, recurrence, and progression in BC patients than traditional strategies, especially when combining miRNA expression with clinicopathological variables. Future studies should focus on validating their use in different cohorts and liquid samples.

The evolution over time and the particularities of treatment of Madelung’s Disease

Madelung’s disease is a pathology characterized by the proliferation of adipose tissue conglomerates with poorly defined margins and surrounding tissue invasion. Over the years the Republic of Moldova’s population had a varied frequency of sickness, mostly were affected men by the disease. A retrospective study was conducted to determine the disease data of the patients affected by the Madelung’s disease treated at IMSP IMU, comparing sex, age, class of affection and geographic distribution during the 1977—1990 and 2011—2021 years.

The poor prognosis of lacrimal gland adenocarcinoma: a clinical study and literature review

PurposeThe incidence of lacrimal gland adenocarcinoma is low. This study was designed to analyze the clinical and prognostic characteristics of lacrimal gland adenocarcinoma.MethodsThis was a clinical study and literature review; 25 patients diagnosed with lacrimal gland adenocarcinoma by histopathology were enrolled and their medical history data were collected.ResultsThe incidence of bone destruction and surrounding tissue invasion was 52% and 44%, respectively. The incidence of distant metastasis of lacrimal gland adenocarcinoma was about 50%. The 5-year overall survival rate of death or metastasis was 33.5%. Age, sex, laterality, tumor size, pathology type, bone destruction, nerve or perineural invasion, invasion of peripheral tissue, T stage, AR, Her-2 and treatment had no significant correlation with lacrimal adenocarcinoma’s prognosis (P > 0.05), while the higher expression of Ki-67 may have higher risk of death or metastasis (P = 0.020).ConclusionThe incidence of bone destruction and distant metastasis of lacrimal adenocarcinoma is high and the imaging examination is necessary to assess the risk of distant metastasis. The 5-year survival rate of death or metastasis is 33.5% and the high expression of Ki-67 predicts poor prognosis of lacrimal adenocarcinoma.

Clinicopathological characteristics and prognostic factors in axial chondroblastomas: a retrospective analysis of 61 cases and comparison with extra-axial chondroblastomas

BackgroundA comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB).MethodsA retrospective review of our institution’s local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin.ResultsACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival.ConclusionThere may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population.

Abstract 2675: Vactosertib combined treatment with T1-44, a PRMT5 activity inhibitor, improves the survival and inhibits tumor invasion of murine pancreatic cancer model

Abstract Pancreatic cancer is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate. Heterogeneity, difficulty in diagnosis, and rapid metastatic progression are the causes of high mortality in pancreatic cancer. Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers, and these patients have a worse prognosis. Therefore, PRMT5 as an anti-cancer target has gained considerable interest. In this study, we investigated whether inhibition of PRMT5 activity was synergistic with blockade of TGF-β1 signaling, which plays an important role in the construction of the desmoplastic matrix and invasiveness in pancreatic cancer and induces therapeutic vulnerability. Compared with T1-44, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival. RNA sequencing analysis of mouse tumors revealed that the combination of T1-44 and vactosertib significantly altered the expression of genes involved in cancer progression, such as cell migration, extracellular matrix, and apoptotic processes. These data demonstrate that the combination therapy of T1-44 with vactosertib is synergistic for pancreatic cancer, suggesting that this novel combination therapy has value in the treatment strategy of patients with pancreatic cancer. Citation Format: Eunji Hong, Sujin Park, Seok Hee Park, Nick B. La Thangue, Seong-Jin Kim. Vactosertib combined treatment with T1-44, a PRMT5 activity inhibitor, improves the survival and inhibits tumor invasion of murine pancreatic cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2675.

Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate. Heterogeneity, difficulty in diagnosis, and rapid metastatic progression are the causes of high mortality in pancreatic cancer. Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers, and these patients have a worse prognosis. Recently, PRMT5 as an anti-cancer target has gained considerable interest. In this study, we investigated whether inhibition of PRMT5 activity was synergistic with blockade of TGF-β1 signaling, which plays an important role in the construction of the desmoplastic matrix in pancreatic cancer and induces therapeutic vulnerability. Compared with T1-44, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor Vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival. RNA sequencing analysis of mouse tumors revealed that the combination of T1-44 and Vactosertib significantly altered the expression of genes involved in cancer progression, such as cell migration, extracellular matrix, and apoptotic processes. In particular, the expression of Btg2, known as a tumor suppressor factor in various cancers, was markedly induced by combination treatment. Ectopic overexpression of Btg2 inhibited the EMT response, blocking cell migration, and promoted cancer cell death. These data demonstrate that the combination therapy of T1-44 with Vactosertib is synergistic for pancreatic cancer, suggesting that this novel combination therapy has value in the treatment strategy of patients with pancreatic cancer.

Preoperative surgical risk assessment of meningiomas: a narrative review based on MRI radiomics.

Meningiomas are one of the most common intracranial primary central nervous system tumors. Regardless of the pathological grading and histological subtypes, maximum safe resection is the recommended treatment option for meningiomas. However, considering tumor heterogeneity, surgical treatment options and prognosis often vary greatly among meningiomas. Therefore, an accurate preoperative surgical risk assessment of meningiomas is of great clinical importance as it helps develop surgical treatment strategies and improve patient prognosis. In recent years, an increasing number of studies have proved that magnetic resonance imaging (MRI) radiomics has wide application values in the diagnostic, identification, and prognostic evaluations of brain tumors. The vital importance of MRI radiomics in the surgical risk assessment of meningiomas must be apprehended and emphasized in clinical practice. This narrative review summarizes the current research status of MRI radiomics in the preoperative surgical risk assessment of meningiomas, focusing on the applications of MRI radiomics in preoperative pathological grading, assessment of surrounding tissue invasion, and evaluation of tumor consistency. We further analyze the prospects of MRI radiomics in the preoperative assessment of meningiomas angiogenesis and adhesion with surrounding tissues, while pointing out the current challenges of MRI radiomics research.

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy.

ObjectiveChondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients.MethodsImmunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features.ResultsTAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan–Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance.ConclusionThese data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

Y-box binding protein-1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma.

Chordomas are rare bone tumors with a poor prognosis and no approved targeted therapy. Y‐box binding protein‐1 (YBX1) promotes tumor growth, invasion and drug resistance. However, the role of YBX1 in chordoma is unclear. In this study, we examined the expression of YBX1 using immunohistochemistry and found that YBX1 was significantly upregulated in 32 chordoma tissues compared to distant normal tissues. In addition, YBX1 upregulation was associated with surrounding tissue invasion, recurrence and poor prognosis. Biological function studies demonstrated that YBX1 promoted cell proliferation and invasion, accelerated G1/S phase transition, and inhibited apoptosis. Further investigation revealed that YBX1 enhanced epidermal growth factor receptor (EGFR) transcription by directly binding to its promoter in chordoma cells. YBX1 regulated protein expression of p‐EGFR, p‐AKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1‐induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

Expression of Kif5b protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma.

Kinesin family member 5b (Kif5b), a conventional kinesin, mainly participates in lysosome and mitochondria transportation. Some studies have indicated that Kif5b may be associated with the development of a variety of tumors. However, the role Kif5b plays in oral squamous cell carcinoma (OSCC) has yet to be determined. Our study aimed at investigating the expression level of Kif5b in primary OSCC and discussing its clinical significance in patients' outcomes. We measured Kif5b expression in 82 OSCC tissue samples with immunohistochemistry. The associations between the expression level of Kif5b and clinicopathological characteristics as well as patients' survival were statistically assessed. Kif5b level was significantly associated with tumor size (p=0.034), histological differentiation (p=0.028), disease recurrence (p=0.018), surrounding tissue invasion (p=0.045), recurrence time (p=0.036) and survival status (p=0.030). Kaplan-Meier cumulative survival analyses indicated that high expression of Kif5b was linked to worse overall survival (p=0.0112) and disease-free survival (p=0.0085). The univariate and multivariate Cox proportional hazard analysis further identified the expression status of Kif5b as an independent variable that correlated with patients' survival and recurrence. Furthermore, in 54 early-stage, clinically node negative OSCC patients, Kif5b expression were correlated with histological differentiation (p=0.034), disease recurrence (p=0.038) and surrounding tissue invasion (p=0.029). Univariate and multivariable logistic regression results showed that only Kif5b expression level could influence the probability of recurrence. Our results reveal that Kif5b expression is associated with poor clinical outcome in OSCC and even in early-stage, clinically node negative OSCC and may be a potential target for OSCC treatment.

Expression of integrin αvβ3, CXC chemokine receptor 4 and CXC chemokine receptor 7 and their relationship with lymph node metastasis in squamous cell carcinoma of head and neck

Objective: To investigate the expression of integrin αvβ3, CXC chemokine receptor (CXCR)4 and CXCR7 and their relationship with lymph node metastasis in squamous cell carcinoma of head and neck (SCCHN). Methods: The expression of integrin αvβ3, CXCR4 and CXCR7 was detected by immunohistochemistry SABC in 92 cases of primary SCCHN, metastatic lymph node, normal oral mucosa tissues and normal lymph nodes. Results: The positive rate of the expression of integrin αvβ3, CXCR4 and CXCR7 was 75% (69/92), 81%(75/92) and 76%(70/92), respectively in primary SCCHN, and was 82%(75/92), 76%(70/92) and 65%(60/92), respectively in metastatic lymph node. The expression of integrin αvβ3 and CXCR4 in primary SCCHN (r=0.813, P<0.05) and lymph node metastasis (r=0.541, P<0.05) was positively correlated. Integrin αvβ3 and CXCR7 expression in primary SCCHN (r=0.683, P<0.05) and lymph node metastasis (r=0.708, P<0.05) was positively correlated. CXCR4 and CXCR7 expression in primary SCCHN (r=0.644, P<0.05) and lymph node metastasis (r=0.707, P<0.05) had a positive correlation. The expression level was associated with tumor size (P=0.040, 0.001, 0.009), lymph node metastasis (P=0.001, 0.000, 0.000) and surrounding tissue invasion (P=0.046, 0.002, 0.001), but not related to age (P=0.097, 0.274, 0.162), gender (P=0.103, 0.309, 0.187). Conclusions: The overexpression of integrin αvβ3, CXCR4 and CXCR7 in primary head and neck squamous carcinoma and metastatic lymph nodes was related to lymph node metastasis. The co-expression of integrin αvβ3, CXCR4 and CXCR7 may play a synergistic role in lymphatic metastasis of SCCHN.

A Zebrafish Live Imaging Model Reveals Differential Responses of Microglia Toward Glioblastoma Cells In Vivo.

Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number of microglia, which promote tumor growth and surrounding tissue invasion. However, it is unclear how microglia and glioma cells physically interact and if there are differences, depending on glioma cell type. Hence, we have developed a novel live imaging assay to study microglia–glioma interactions in vivo in the zebrafish brain. We transplanted well-established human glioblastoma cell lines, U87 and U251, into transgenic zebrafish lines with labelled macrophages/microglia. Our confocal live imaging results show distinct interactions between microglia and U87, as well as U251 glioblastoma cells that differ in number and nature. Importantly these interactions do not appear to be antitumoral as zebrafish microglia do not engulf and phagocytose the human glioblastoma cells. Finally, xenotransplants into the irf8−/− zebrafish mutant that lacks microglia, as well as pharmacological inhibition of the CSF-1 receptor (CSF-1R) on microglia, confirm a prominent role for zebrafish microglia in promoting human glioblastoma cell growth. This new model will be an important tool for drug screening and the development of future immunotherapeutics targeting microglia within glioma.

Risk factors of level Ⅵ lymph node metastasis in cN0 papillary thyroid carcinoma

Objective:To study the risk factors related to level Ⅵ lymph node metastasis in clinical N0 (cN0) papillary thyroid carcinoma (PTC). Method:A total of 107 cases with cN0 PTC treated in the same group were analyzed retrospectively. The frequency and risk factors for level Ⅵ lymph node metastasis in these patients were analyzed. Result:Level Ⅵ lymph node metastasis existed in 51.40% (55/107) cases. In univariate analysis, level Ⅵ lymph node metastasis was associated with age (χ²＝9.090,P<0.01), gender (χ²＝5.061,P<0.05), tumor maximum diameter (χ²＝8.772,P<0.01), tumor multifocality (χ²＝8.120,P<0.01), capsular invasion (χ²＝4.960,P<0.05), and surrounding tissue invasion (χ²＝3.858,P<0.05), but not with nodular goiter or Hashimoto's thyroiditis. Multivariate logistic analysis indicated that age,tumor maximum diameter, multifocal tumors and surrounding tissue invasion were independent risk factors for level Ⅵ lymph node metastasis. Conclusion:A high risk level Ⅵ lymph node metastasis exists in DTC with clinical N0. Prophylactic level Ⅵ neck dissection is strongly recommended in patients with PTC who are younger, tumor size more than 2 cm, multifocal tumor and surrounding tissue invasion.

Clinical Analysis of Familial Nonmedullary Thyroid Carcinoma.

To analyze the clinical characteristics of familial nonmedullary thyroid carcinoma (FNMTC), in order to provide evidence for early diagnosis and treatment. We retrospectively investigated the inpatients between September 2006 and September 2013 in the First Bethune Hospital of Jilin University, in which 78 patients with FNMTC from 31 families were analyzed by a comparison with 3445 control cases from the patients with sporadic nonmedullary thyroid carcinoma (SNMTC). There was no significant difference in gender, age, and tumor size between FNMTC and SNMTC patients. However, the characteristics of disease in multifoci, neck lymph node metastasis, invasion to the surrounding tissues, and coexistence with Hashimoto disease in two types of cancer patients show significant difference. They are: multifoci: 71.8% (56/78) in FNMTC versus 46.3% (1595/3445) in SNMTC; neck lymph node metastasis: 52.6% (41/78) in FNMTC versus 33.3% (1148/3445) in SNMTC; surrounding tissue invasion: 64.1% (50/78) in FNMTC versus 48.5% (1670/3445) in SNMTC; coexistence with Hashimoto disease: 30.8% (24/78) in FNMTC versus 20.0% (689/3445) in SNMTC. Lymph node metastasis, multifoci, invasion to the surrounding tissues, and combination with chronic lymphocytic thyroiditis are the main features of FNMTC, which suggests the extent of the operation for FNMTC patients should be amplified properly.

Clinical value of delayed 18F-FDG PET/CT imaging after diuresis in male patients with locally recurrent rectal cancer

Objective To explore the diagnostic value of delayed 18F-FDG PET/CT pelvic imaging after forced diuresis in detecting male patients with locally recurrent rectal cancer. Methods Thirty-two male patients (32-79 years) with clinically suspicious recurrences of rectal cancer were retrospectively analyzed. All patients underwent a standard 18F-FDG PET/CT followed by a delayed pelvic imaging after 2.5 h of administration of 20 mg furosemide intravenously and extra water intake of 500 ml at least. Final diagnosis was made by pathology or clinical follow-up (>10 months). Diagnostic efficiency of 18F-FDG PET/CT standard and delayed pelvic images were calculated and compared. χ2 test was used for data analysis. Results A total of 25 patients were diagnosed with recurrent rectal cancer, including 10 cases with invasion of surrounding tissue, and 5 cases with metastases. Among the 7 patients without local recurrences, 2 had distant metastases. The sensitivity, specificity, and accuracy of standard FDG PET/CT were 92.0%(23/25), 3/7, 81.2%(26/32), respectively. The corresponding values of the delayed imaging were 96.0%(24/25), 6/7, and 93.8%(30/32), respectively. The specificity of delayed imaging was higher than that of standard FDG PET/CT (χ2=14.333, P 0.05). The urinary bladder activity reached or approached the background during the delayed imaging. Twenty-two malignant lesions of surrounding invasion were confirmed. The positive rate of delayed imaging was higher than that of standard FDG PET/CT: 95.5%(21/22) vs 63.6%(14/22); χ2=6.400, P<0.05. Conclusions 18F-FDG PET/CT delayed pelvic imaging after diuresis and hydration is useful for eliminating the artifacts from urinary bladder activity, and for detecting the invasion to the rectal surrounding tissue more effectively. It could be a supplement to standard FDG PET/CT. Key words: Rectal Neoplasms; Neoplasm recurrence, local; Diuresis; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Chemokine receptor 7 enhances cell chemotaxis and migration of metastatic squamous cell carcinoma of head and neck through activation of matrix metalloproteinase-9.

The mechanisms leading to squamous cell carcinoma of head and neck (SCCHN) metastasis are not fully understood. Although evidence shows that the chemokine receptor 7 (CCR7) and its ligand CCL19 may regulate tumor dissemination, their role is not clearly defined in SCCHN. Matrix metalloproteinases break consisting of tissue barrier to the surrounding tissue invasion and metastasis by destroying the balance of matrix degradation of the basement membrane of tumor cells and extracellular matrix (ECM). We used chemotaxis and migration assays, western blotting, gelatin zymography, actin polymerization assay, immunofluorescence staining and immunohistochemical analysis to explore whether MMP-9 can be activated by CCL19 (CCR7's ligand) and its role in SCCHN. The experiments were performed in the metastatic SCCHN cell line PCI-37B after pre-incubation of the cells with CCL19 and SB-3CT (inhibitor of MMP-9). Our results demonstrated that CCR7 favors PCI-37B cell chemotaxis and migration, upregulation of MMP-9 protein and motivates the activity of MMP-9 protein, induces reorganization of the actin cytoskeleton and upregulation of MMP-9 protein. SB-3CT can block all these effects. Collectively, our data indicated that CCR7 regulates cell chemotaxis and migration via MMP-9 in metastatic SCCHN, and these results provide a basis for new strategies in preventing metastases of SCCHN.

MCM3 Protein Expression in Follicular and Classical Variants of Papillary Thyroid Carcinoma

Minichromosome maintenance (MCM) proteins are needed as licensors in the DNA replication of eukaryotic cells and transcriptional control of MCM genes has critical role in the regulation of MCM functions. Different MCM protein family members are proposed as diagnostic or prognostic markers in various cancers due to their increased proliferative potential. Among MCM family members, minichromosome maintenance protein 3 (MCM3) expressions in both mRNA and protein levels were shown to be associated with papillary thyroid carcinoma (PTC). But, the usability of MCM3 in some histological variants of PTC might be controversial due to tissue specific molecular heterogeneities. In follicular variant of papillary thyroid carcinoma (FVPTC), a number of genes including MCM3 were shown to be differentially expressed which were specific to this kind of variant. Using immunohistochemistry method, MCM3 protein expression levels were compared in FVPTC, classic variant of papillary thyroid carcinoma (CVPTC), and multi-nodular goiter (MNG) tissues in a group of 32 cases. There was meaningful differences between MNG vs. FVPTC (p = 0.016) and MNG vs. CVPTC (p = 0.019) while there was no significant difference in the comparison FVPTC vs. CVPTC (p = 0.15). Four of the 5 CVPTC cases having surrounding tissue invasion had high expression values. For FVPTC and CVPTC, MCM3 protein expression results were parallel to our previous mRNA expression study while there was downregulation in protein expression despite the increased expression of MCM3 mRNA in MNG suggesting tissue-specific post-transcriptional events in benign thyroid neoplasms of which should be focused on. Moreover, the relatively lower MCM3 protein expression in FVPTC comparing to CVPTC could be due to a different tumorigenic pathway favored in this type of tissue.

Aspergillosis in Cats

Aspergillosis is a sporadic mycosis that occurs worldwide in mammals and birds and leads to a usually chronic, and only rarely acute, disease that mainly affects the nasal cavity and sinuses. Aspergillus species infections are commonly associated with predisposing local or systemic factors. Local disease can spread and involve the central nervous system or the lungs. Some Aspergillus species can also disseminate, causing systemic infections. In contrast to dogs, in which (nasal) aspergillosis is relatively common, aspergillosis is rare in cats, but considered an emerging infection. There are two clinical forms of aspergillosis in cats, the sinonasal form (characterised by signs of chronic nasal infection) and the newly emerging, more invasive sino-orbital form (characterised by signs of orbital and surrounding tissue invasion). Sino-orbital involvement has been described now in approximately half of the reported cases. Treatment should consist of local and systemic antifungal therapy.

SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

Background and AimsConsidering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs.MethodsRetrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR.ResultsUnivariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41–5.99, P = 0.004) and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04–7.16, P = 0.041) were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98–3.64, P = 0.059). In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further.ConclusionOur results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for primary GIST patients.