Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth.

As an important second messenger, calcium (Ca2+) regulates a wide variety of physiological processes. Disturbance of intracellular calcium homeostasis implicated in the occurrence of multiple types of diseases. Orai1 is the major player in mediating store-operated calcium entry (SOCE) and regulates calcium homeostasis in non-excitable cells. Over-expression and activation of Orai1 have been reported in breast cancer. However, its molecular mechanisms are still not very clear. Here, we demonstrated that Nucleolin (NCL) was a novel interacting partner of Orai1. NCL is a multifunctional nucleocytoplasmic protein and is upregulated in human breast tumors. The binding of C-termini of NCL (NCL-CT) to N-termini of Orai1 (Orai1-NT) is critical for mediating calcium influx and proliferation of breast cancer cells. Blocking the NCL-Orai1 interaction by synthesized Orai1 peptide can effectively reduce the intracellular calcium influx and suppress the proliferation of breast cancer cells in vitro and in vivo. Our findings reveal a novel activation mechanism of Orai1 via direct interaction with NCL, which may lead to calcium homeostasis imbalance and promote the proliferation of breast cancer cells. Blocking NCL-Orai1 interaction might be an effective treatment of breast cancer.

Gastric calcifying fibrous tumors: Computed tomography findings and clinical manifestations.

ABSTRACT: To retrospectively analyze the computed tomography (CT) findings and clinical manifestations of gastric calcifying fibrous tumor (CFTs).The features of 7 cases with pathologically proven gastric CFTs who had undergone CT were assessed, including tumor location, contour, growth, degree of enhancement, calcification and clinical data. In addition, the size and CT value of each lesion were measured. The mean values of these CT findings and clinical data were statistically analyzed only for continuous variables.Four patients were female and three were male (mean age: 33.3 years; range: 22 ∼ 47 years). Nonspecific clinical symptoms: abdominal pain and discomfort were observed in four cases and the CFTs were incidentally detected in the other three cases. Regarding tumor markers, lower ferritin levels were observed in three female patients. All of the gastric CFTs were solitary and mainly located inside the body; they were in round or oval shape and exhibited endophytic growth. Gastric CFTs are usually small sized and could contain confluent and coarse calcifications; cyst, necrosis, ulcer, bleeding and surrounding lymphadenopathy were not found in any of the cases. Unenhanced CT values of gastric CFTs were higher than those of same-transect soft tissue. Mild-to-moderate enhancement in the arterial phase and progressive enhancement in the portal venous phase were mainly noted.A gastric mass with a high unenhanced CT attenuation value, confluent and coarse calcifications and mild-to-moderate enhancement could prompt a diagnosis of gastric CFT. In addition, (1) being young- or middle-aged, (2) having relatively low ferritin levels, and (3) tumor located in the gastric body have critical reference value for diagnosis of gastric CFT.

Synchronous multiple primary gallbladder and gastric malignancies: Report of two cases and review of the literature.

Multiple primary malignancies (MPM) are rare. In particular, synchronous gallbladder and gastric malignancies are extremely rare, are associated with a concealed onset and atypical symptoms, and are highly likely to be overlooked or misdiagnosed. The clinical data of two patients with synchronous gallbladder and gastric malignancies are herein reported and integrated with the relevant literature to retrospectively analyze and summarize the pathogenesis and clinical characteristics of MPM. Case 1 was a male 46-year-old patient who underwent laparoscopic cholecystectomy, and succumbed to extensive tumor metastasis 2 months after the operation. Case 2 was an 80-year-old female patient who was treated with distal gastrectomy for gastric cancer, cholecystectomy, gastrojejunostomy and dissection of 5 suprapyloric, 6 subpyloric, 7 left gastric and 8 common hepatic artery lymph nodes, and succumbed to multiple organ failure induced by extensive tumor invasion within 1 week after the operation. Clinical physicians must pay closer attention to early symptoms of MPM in order to make an accurate diagnosis, perform timely radical surgical treatment and achieve favorable therapeutic outcomes, in terms of significantly increasing long-term patient survival rates.

Malignant gastrointestinal neuroectodermal tumor: A case report and review of the literature.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare soft tissue sarcoma, previously referred to as clear cell sarcoma-like gastrointestinal tumor (CCSLGT) and also commonly reported in the literature as clear cell sarcoma of the gastrointestinal tract (CCS-GI). The current study reports a case of GNET arising in the stomach of a 17-year-old male, who presented with symptoms of fatigue, anemia and low temperature. Examination with positron emission tomography-computed tomography revealed a soft tissue mass in the gastric antrum. Subsequently, radical distal gastric resection was performed, and the mass measured 6.0×4.0×3.5 cm3. Histopathological analysis revealed that the tumor cells were arranged in nests and focally formed fascicular, pseudopapillary, pseudoalveolar and rosette-like growth patterns. Osteoclast-like giant cells were also observed. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin and BCL-2, and negative for HMB45, Melan-A, CD117, CD34 and CD99. Additionally, the osteoclast-like giant cells were positive for CD68. Fluorescence in situ hybridization demonstrated EWSR1 gene rearrangement. After 10 months of follow-up, no evidence of recurrence or metastasis was observed. As GNET is currently classified differently and under various names in the literature, the information provided by this case study and review is predicted to be useful towards the accurate diagnosis, treatment and prognosis of this rare tumor type.

[Clinicopathological analysis of 64 case of angioimmunoblastic T-cell lymphoma].

OBJECTIVE: To explore the clinical and pathological characteristics of angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-four cases of AITL were retrospectively analyzed by histopathological and immunohistochemical methods. RESULTS: There were 35 men and 29 women, the median age was 59 years (range, 25-84 ys). AITL typically presented with advanced stage, generalized lymphadenopathy, hepatosplenomegaly and systemic symptoms. Morphologically, the lymph nodes showed partial or total obliteration of the normal architecture by a polymorphic infiltration of lymphocytes, and by proliferation of follicular dendritic cells and that of high endothelial venules. Most cases contained a monoclonal T-cell population as well as clonal cytogenetic abnormalities. Immunophenotype analysis showed that neoplastic cells expressed the following markers: CXCL13 (positive rate 95.3%), PD-1 (positive rate 75.0%), CD10 (positive rate 25.0%), Bcl- 6 (positive rate 40.0%), CD2 (positive rate 96.0%), CD3 (positive rate 95.0%), CD4 (positive rate 84.0%), CD5 (positive rate 73.0%), EBER (positive rate 39.5%) and Ki-67 (average positive rate 55.0%), and frequently showed aberrant loss or reduced expression of CD7 and CD8. CONCLUSION: The neoplastic cells of AITL showed features of CD4+ TFH, with peculiar clinical features. Peripheral T-cell lymphomas with a follicular growth pattern may show overlapping features with focal AITL.

[Misdiagnosis of 3 cases lymphoma due to misjudgement of immunohistochemistry].

OBJECTIVE: To recognize the importance of analyzing the result of immunohistochemical staining correctly. METHOD: Review of the three misdiagnosed cases lymphoma and exploring the causes of misdiagnosis through reviewing their clinics, histopathology and immunohistochemistry. RESULTS: Case 1 of lymphocyte rich classical Hodgkin's lymphoma (LRCHL) was misdiagnosed as follicular lymphoma (FL) initially, the RS cells were overlooked morphologically and wrongly determined BCL-2 and CD20-positive cells as tumor cells immunohistochemically; also once misdiagnosed as nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) because the CD20-negative RS misjudged cells as the positives. Case 2 of AML tumor cells expressed TdT, CD7 and CD43 unspecifically, which misdiagnosed as T-cell lymphoblastic lymphoma (T-LBL). Case 3 of type B1 thymoma was misdiagnosed as T-LBL, because CK wasn't expressed satisfactorily resulting in neglecting neoplastic epithelial cells, and lymphocytes in the background were TdT and CD99-positive. CONCLUSION: The diagnosis of lymphoma should be based on morphology, immunohistochemistry, clinics, and genetics. Moreover, the correct judgment of immunohistochemical staining is essential to make right diagnosis.