SMARCA4­deficient non­small cell lung cancer with an EGFR mutation: A case report.

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4)-deficient non-small cell lung cancer (dNSCLC) is a rare malignant tumor that originates in the lungs. It occurs more frequently in male smokers, and the epidermal growth factor receptor (EGFR) gene is often mutation-free. In the present study, the case of a 60-year-old, non-smoking female patient diagnosed with SMARCA4-dNSCLC is reported. Biopsy of the tumor showed solid flaky, nest-like infiltrating growth. Immunohistochemistry revealed the following: SMARCA4/BRG1(-), SMARCB1/INI-1(+), cytokeratin7 (+), cytokeratin 5.2 (+), CK5/6(+) and calretinin(+). The Ki-67 positivity index was 75%, and the thyroid transcription factor-1, NapsinA, p40, nuclear protein in testis, CD34, Sal-like protein 4, SRY-box transcription factor 2 and synaptophysin were negative. Molecular analysis showed mutations in both EGFR and TP53. The pathological diagnosis was SMARCA4-dNSCLC with an EGFR gene mutation. The present case report could be used for broadening the pathological diagnosis of SMARCA4-dNSCLC and for selecting appropriate treatment approaches.

Rare urachal mucinous cystic tumor of low malignant potential with peritoneal pseudomyxoma: A case report.

Mucinous cystic tumors of low malignant potential (MCTLMP) are rare urachal neoplasms. The morphological characteristics and clinical prognosis of MCTLMP is similar to that of mucinous cystic tumors occurring in the ovary and appendix. After complete resection, almost no cases of recurrence or metastasis have been reported. Because MCTLMP is rare, it may be missed in the clinic. MCTLMP can lead to the formation of pseudomyxoma peritonei (PMP), which manifests as the widespread production of mucus in the abdominal cavity and makes the disease complex or difficult to diagnose. At present, only 3 cases of MCTLMP with PMP have been reported in the literature. In the present study a fourth case of urachal MCTLMP in a 74-year-old male that resulted in widespread PMP is presented. Initially, a multilocular cystic lesion was revealed in the urachal duct area at the anterior upper margin of the bladder after a patient, experiencing lower abdominal pain, was imaged. As revealed using light microscopy, the cyst was lined with a mucous columnar epithelium, and part of the epithelium indicated pseudolamellar hyperplasia and papillary structures. The cells indicated mild atypia and low mitotic activity. There was no stromal infiltration of tumor cells, and a large amount of mucous exudate was observed. As preoperative computed tomography examination suggested the presence of a large amount of ascites and there were increased levels of blood tumor markers, carcinoembryonic antigen and carbohydrate antigen 125, clinicians considered that the diagnosis maybe a malignant tumor of the urachal gland with peripheral dissemination. However, the diagnosis of MCTLMP with PMP was confirmed by histopathological examination. The mass was completely removed, along with part of the peritoneum and bladder wall as these were within the tumor margin. The appendix appeared normal during surgery. A one off dose of intraperitoneal infusion chemotherapy with 1,000 mg 5-fluorouracil was performed after surgery. No recurrence was observed during the 8-month follow-up period.

Comparison of surface properties, cell behaviors, bone regeneration and osseointegration between nano tantalum/PEEK composite and nano silicon nitride/PEEK composite.

Both tantalum (Ta) and silicon nitride (SN) exhibit osteogenic bioactivity and antibacterial property. In addition, as a biomaterial for bone repair, polyetheretherketone (PEEK) has outstanding biocompatibility and mechanical performances while it is biologically inert. In this study, by blending PEEK with Ta and SN nanoparticles, respectively, Ta/PEEK composite (TPC) and SN/PEEK composite (SPC) were fabricated for load-bearing bone repair. The surface roughness, hydrophilicity and surface energy of TPC containing Ta nanoparticles were higher than SPC containing SN nanoparticles and PEEK. In addition, TPC with Ta nanoparticles exhibited low antibacterial property while SPC with SN nanoparticles showed high bacterial property. Moreover, the MC3T3-E1 cells responses (e.g. proliferation and differentiation) to TPC was the highest while PEEK was the lowest in vitro. Furthermore, new bone formation and osseointegration for TPC was the highest while PEEK was the lowest in vivo. In conclusion, compared with PEEK, addition of Ta and SN nanoparticles into PEEK fabricated bioactive composites of TPC and SPC with optimized surface property, which played crucial roles in inducing cellular response/bone regeneration. Although the osteogenic activity of SPC was lower than TPC, SPC exhibited osteogenic activity and good antibacterial property, which could prevent infection from bacterial. Therefore, SPC would have better potential for bone substitute.

SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through regulation of the PI3K/Akt pathway.

SIRT3 is involved in aging-related diseases including cancer, but its role in prostate cancer and detailed regulatory function are not known. We found that SIRT3 was moderately down-regulated in prostate carcinomas. Overexpression of SIRT3 by lentiviral transfection inhibited prostate cancer growth both in vitro and in vivo, whereas knockdown of SIRT3 increased prostate tumor growth. Mechanistically, the tumor suppression effect of SIRT3 was achieved via its inhibition of the PI3K/Akt pathway. Notably, upregulation of SIRT3 suppressed the phosphorylation of Akt, leading to the ubiquitination and degradation of oncoprotein c-MYC; this could be attenuated by constitutive activation of PI3K/Akt signaling. Collectively, our results unveiled SIRT3's tumor suppressive function and the underlying mechanism in prostate cancer, which might provide therapeutic implications for the disease.

Micropapillary component in colorectal carcinoma is associated with lymph node metastasis in T1 and T2 Stages and decreased survival time in TNM stages I and II.

Colorectal carcinoma with a micropapillary component (MP) is an exceptionally aggressive variant, but has never been investigated in terms of survival analysis. Thirty colorectal carcinomas with a MP were identified from a series of 221 colorectal carcinomas. Carcinomas with and without a MP were compared in terms of histologic and immunohistochemical markers. Colorectal carcinoma with a MP seemed to have a lower differentiation status, increased tumor budding, more frequent lymphovascular and perineural invasion, more frequent lymph node metastasis, higher tumor node metastasis (TNM) stage, and less nuclear beta-catenin staining (P<0.05). Further analysis revealed that the presence of a MP predicted more frequent lymph node metastasis in T1 and T2 stages but not in T3 and T4 stages. Five-year survival rates for patients with a MP and those without were 50% and 73%, respectively. Furthermore, in TNM stages I and II, but not in TNM stages III and IV, a MP was an unfavorable prognostic variable. A MP was demonstrated to be an independent unfavorable prognostic indicator in TNM stages I and II by the multivariate Cox proportional hazard model. Colorectal carcinoma with a MP should be distinguished from colorectal carcinoma of conventional histologic type.

[Primary malignant tumor of the appendix: clinicopathological analysis of 22 cases].

OBJECTIVE: To investigate the clinicopathological and immunohistochemical features of primary malignant tumor of the appendix. METHODS: The clinical data were reviewed; and histopathological and immunohistochemical features were analyzed in 22 cases with primary malignant tumor of the appendix. RESULT: In 22 cases of primary malignant tumor of the appendix, 19 cases were carcinoid and 3 were adenocarcinoma. Immunohistochemistry showed that the carcinoid was positively reacted to the neuroendocrine markers, and the adenocarcinoma was negatively reacted to the neuroendocrine markers. CONCLUSION: Immunohistochemistry is useful in diagnosis of primary malignant tumor of the appendix, a rare type of cancer.

Classification based on the combination of molecular and pathologic predictors is superior to molecular classification on prognosis in colorectal carcinoma.

PURPOSE: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage. EXPERIMENTAL DESIGN: Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221 colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model. RESULTS: Six pathologic predictors and four molecular predictors were of significant prognostic value (P

IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.

Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formation activity and induce apoptosis in RKO and SW620 cells. Correlation analysis between the expression of IGFBP7 in CRC tissue and the prognosis in 218 patients showed that high expression of IGFBP7 was associated with favorable prognosis. Based on above results, we conclude that IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.

IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1.

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.

[Influence of clinical and pathomorphological parameters on prognosis in colon carcinoma and rectal carcinoma].

OBJECTIVE: To investigate the effects of clinical and pathomorphological parameters on the prognosis of colon carcinoma and rectal carcinoma. METHODS: Univariate and multivariate COX proportional hazard models were used to study the effects of the clinical and pathomorphological factors on the prognosis in 101 cases of colon carcinoma, 219 of rectal carcinoma and 137 of rectal carcinoma under curative resections. RESULT: By using univariate analysis, we identified that lymph node metastasis and distant metastasis were the common prognostic factors for both colon carcinoma and rectal carcinoma. Smoking, deep infiltration, chemotherapy and serum albumin concentration were the uncertain prognostic factors for colon carcinoma. Signet-ring cell carcinoma, larger tumor size (>6 cm), deep infiltration, lack of radical surgery, and advanced TNM stage were the exclusive adverse prognostic factors for rectal carcinoma. Further studies showed that the adverse prognostic factors for the rectal carcinoma under curative resection included deep infiltration, lymph node metastasis, vessel invasion, less of peritumoral lymphocyte infiltration, lack of Crohn's like reactivity, high level of tumor budding, advanced TNM stage and positive urine glucose. By using multivariate analysis based on a COX proportional hazard model, it was identified that smoking, lymph node metastasis and serum albumin concentration were independent prognostic factors for colon carcinoma; advanced TNM stage, distant metastasis and palliative surgery for rectal carcinoma; and vessel invasion, lymph node metastasis and urine glucose for rectal carcinoma under curative resections. CONCLUSION: The various clinical and pathomorphological parameters show different prognostic value for colon carcinoma, rectal carcinoma and rectal carcinoma under curative resections.