KIF3A Inhibits NPC Proliferation, Migration and Invasion By Interacting With β-Catenin To Suppress Its Nuclear Accumulation

Background Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumour that is prevalent in Southern China and other Southeast Asian countries. In previous studies, Kinesin Family Member 3A (KIF3A) was shown to play a dual role in cancers. However, the biological role of KIF3A in NPC and the underlying mechanism have not been reported. Methods The KIF3A mRNA and protein expressions in NPC were analyzed by qRT-PCR (Quantitative real-time polymerase chain reaction), Western blotting and immunohistochemistry. CCK-8, EDU incorporation assay, Colony formation, cell cycle assay, Wound-Healing Assay, Transwell verified KIF3A regulates the proliferation, migration, invasion of NPC cells. The in vivo effect of KIF3A on proliferation was elucidated with a xenograft mouse model. COIP (Co-immunoprecipitation) assay showed KIF3A interacts with β-catenin. Confocal microscopy colocalization assay confirmed colocalization of KIF3A and β-catenin in NPC cells. Nuclear and cytoplasmic extraction assays were performed to analyze the distribution of β-catenin in the nuclei and cytoplasm. Results In this study, we found that KIF3A interacts with β-catenin, suppressing the intranuclear aggregation of β-catenin, then inactivating the Wnt/β-catenin signaling pathway as well as the downstream cell cycle factors and EMT signal to inhibit NPC proliferation, migration, and invasion. Conclusions These findings suggest that KIF3A interacts with β-catenin and attenuates the malignant progression of NPC by inhibiting β-catenin intranuclear aggregation. KIF3A may be a promising therapeutic target for NPC patients.

Comparative clinicopathological and immunohistochemical study of micronodular thymoma and micronodular thymic carcinoma with lymphoid stroma

AimTo elucidate the clinicopathological and immunohistochemical characteristics of micronodular thymomas (MNTs) and micronodular thymic carcinomas (MNCs) with lymphoid stroma.MethodsWe examined four cases of MNTs and three cases of MNCs pathologically and immunohistochemically.ResultsThere were prominent cystic changes infive of the seven cases. The neoplasms contained epithelial tumour cells arranged in a micronodular growth pattern lined by cystic walls and separated by abundant lymphoid stroma. Only the tumour cell component of MNCs showed signs of malignancy characterised by cytological atypia and increased mitotic activity. Neoplastic MNC epithelial cells showed strong positivity for CD5 and CD117. However, no immature lymphocytes (TdT-positive and CD99-positive) were present in and around the tumour nodules. None of the patients died or suffered from disease due to MNTs or MNCs.ConclusionMNTs and MNCs are rare and less aggressive forms of thymic tumours and can be differentially diagnosed by immunohistochemistry.

Thymic carcinoma with extrinsic occlusion of the left anterior descending artery: a distinctive case of myocardial infarction in a young woman

Background Thymic epithelial tumour (TET) is the most common tumour affecting the anterior mediastinum in adults. The cardiac extension is often limited to the pericardium, and intracardiac extension is rare. We present a unique case of encasement and displacement of the left anterior descending coronary artery by the large mediastinal tumour leading to myocardial ischemia. Case presentation Our patient is a 28-year-old lady with stage 4 TET. She presented with acute chest pain associated with 12-lead ECG changes and a significant rise in serial troponin I. Multimodality cardiac imaging revealed encasement and displacement of the left anterior descending coronary artery by the large mediastinal tumour. CT-FFR demonstrates evidence of ischemia which would account for her acute presentation. Following detailed MDT discussions between cardiologists, oncologists and cardiothoracic surgeons, the decision was made to treat this lady with palliative chemotherapy. Given the extent of the tumour invasion and failure of the initial therapy, her prognosis and the outcome were poor. Conclusions TET could cause atrial compression, myocardial infiltration, and invasion of the pulmonary and caval veins; however, to the best of our knowledge, this is the first case reported of coronary artery displacement and encasement by TET.

Adenomatoid Odontogenic Tumour - The Master of Disguise

Adenomatoid odontogenic tumour, truly coined as one of the masters of disguise of orofacial pathologies, was first reported in the literature by Steen Lands.1 Philipson and Brin used the terminology adenomatoid odontogenic tumour for this pathology with its commonly accepted abbreviation AOT.2 Later on, adenomatoid odontogenic tumour (AOT) name was accepted by the World Health Organization (WHO) in 1971. In 2005, WHO revealed the histological variants of the adenomatoid odontogenic tumour and classified it as a tumour comprised of odontogenic epithelium showing various patterns in histopathologic view within a mature connective tissue stroma.3 It is seldom noticed neoplasm which comprises only 3 % of all the odontogenic tumours. It was commonly found in the maxilla with female predilection and mostly in association with impacted canines.4-6 Adenomatoid odontogenic tumour is an odontogenic epithelial tumour usually seen in females in their second decade of life. The tumour is slow growing in nature which eventually results in painless expansion of jaw. The maxilla is commonly affected than mandible. Being benign in nature, most of the AOT cases usually got treated with conservative surgical enucleation but the greater size of tumour can leave behind an oro-facial defect. To prevent such type of incident, it is important to diagnose them early and treat accordingly. Herewith, we are presenting a case report of adenomatoid odontogenic tumour of mandible in a male patient.

Mimicker of Renal Cell Carcinoma- A Case Report

Oncocytoma is a rare epithelial tumour composed of oncocytes which are epithelial cells with excessive amount of mitochondria. The tumour is most often benign, and diagnosis can be made on the basis of histopathological examination. Here, the authors present a 64-year-old female patient, with complaints of abdominal discomfort and flank pain, along with history of loss of weight and appetite for one month. Radiology showed a left renal mass of measuring 9×7×4.5 cm involving the upper and middle pole suggestive of malignancy. Following which radical nephrectomy was done. Examination of gross specimen showed a fairly circumscribed brownish lesion in the upper and middle pole of left kidney measuring 8.8×7×4.5 cm with a central scar. There was no evidence of hilar and perirenal fat invasion. Histology showed sheets of large polygonal eosinophilic cells with centrally placed nucleus. The differentials were eosinophilic variant of clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma. A panel of Immunohistochemical (IHC) markers was performed for further categorisation and the lesional cells were positive for CD 117 and negative for CD 7 and CD 10. This ruled out the differentials and confirmed oncocytoma, thus ruling out the necessity for chemotherapy.

Tomoelastography for non-invasive detection of ameloblastoma and metastatic neck lymph nodes

Ameloblastoma is a benign epithelial tumour and the most common odontogenic tumour, accounting for about 18% of cases. We present a patient to illustrate the first use of tomoelastography for quantitatively mapping tissue stiffness (shear wave speed) and fluidity (loss angle of the complex shear modulus) in a metastasised ameloblastoma of the left mandible. Tomoelastography maps clearly depicted the extent of the tumour by abnormally high values of stiffness and fluidity (1.73±0.23 m/s, 1.18±0.08 rad) compared with normal values in the contralateral mandible (1.04±0.09 m/s, 0.93±0.12 rad). Abnormal stiffness also revealed metastatic involvement of the neck lymph nodes (1.30±0.03 m/s vs 0.86±0.01 m/s). Taken together, stiffness and fluidity measured by tomoelastography can sensitively detect the presence and extent of bone tumours and metastatic spread to cervical lymph nodes.

1- and 2-Photon Phototherapeutic Effects of Ru(II) Polypyridine Complexes in the Hypoxic Centre of Large Multicellular Tumour Spheroids and Tumour-Bearing Mice

During the last decades, photodynamic therapy (PDT), an approved medical technique, has received increasing attention to treat certain types of cancer. Despite recent improvements, the treatment of large tumors remains a major clinical challenge due to the low ability of the photosensitizer (PS) to penetrate a 3D cellular architecture and the low oxygen concentrations present in the tumour centre. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumour spheroids (MCTSs) with a diameter of 800 µm were used in this work to test a series of new Ru(II) polypyridine complexes as 1-Photon and 2-Photon PSs. These metal complexes were found to fully penetrate the 3D cellular architecture and to generate singlet oxygen in the hypoxic centre upon light irradiation. While having no observed dark toxicity, the lead compound of this study showed an impressive phototoxicity upon clinically relevant 1-Photon (595 nm) or 2-Photon (800 nm) excitation with a full eradication of the hypoxic centre of the MCTSs. Importantly, this efficacy was also demonstrated on mice bearing an adenocarcinomic human alveolar basal epithelial tumour.

1- and 2-Photon Phototherapeutic Effects of Ru(II) Polypyridine Complexes in the Hypoxic Centre of Large Multicellular Tumour Spheroids and Tumour-Bearing Mice

During the last decades, photodynamic therapy (PDT), an approved medical technique, has received increasing attention to treat certain types of cancer. Despite recent improvements, the treatment of large tumors remains a major clinical challenge due to the low ability of the photosensitizer (PS) to penetrate a 3D cellular architecture and the low oxygen concentrations present in the tumour centre. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumour spheroids (MCTSs) with a diameter of 800 µm were used in this work to test a series of new Ru(II) polypyridine complexes as 1-Photon and 2-Photon PSs. These metal complexes were found to fully penetrate the 3D cellular architecture and to generate singlet oxygen in the hypoxic centre upon light irradiation. While having no observed dark toxicity, the lead compound of this study showed an impressive phototoxicity upon clinically relevant 1-Photon (595 nm) or 2-Photon (800 nm) excitation with a full eradication of the hypoxic centre of the MCTSs. Importantly, this efficacy was also demonstrated on mice bearing an adenocarcinomic human alveolar basal epithelial tumour.