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The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene-expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-β signaling pathway. We have identified a subset of 11 genes (13 probe sets) that formed a prognostic gene-expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene-expression changes revealed prominent involvement of the focal adhesion and MAPK signaling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture-microdissected corresponding primary tumor stroma compared with the matched normal lung. Six of these 14 genes could be induced by TGF-β1 in NF. The results establish the prognostic impact of CAF-associated gene-expression changes in NSCLC patients.

Background The cyclin D1 (CCND1) and cyclin D3 (CCND3) are frequently co-overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here we examine their differential roles in PDAC. Results CCND1 and CCND3 expression were selectively suppressed by shRNA in PDAC cell lines with expression levels of equal CCND1 and CCND3 (BxPC3), enhanced CCND1 (HPAC) or enhanced CCND3 (PANC1). Suppression of cell proliferation was greater with CCND3 than CCND1 downregulation. CCND3 suppression led to a reduced level of phosphorylated retinoblastoma protein ( Ser795 p-Rb/p110) and resulted in decreased levels of cyclin A mRNA and protein. A global gene expression analysis identified deregulated genes in D1- or D3-cyclin siRNA-treated PANC1 cells. The downregulated gene targets in CCND3 suppressed cells were significantly enriched in cell cycle associated processes (p < 0.005). In contrast, focal adhesion/actin cytoskeleton, MAPK and NF B signaling appeared to characterize the target genes and their interacting proteins in CCND1 suppressed PANC1 cells. Conclusions Our results suggest that CCND3 is the primary driver of the cell cycle, in cooperation with CCND1 that integrates extracellular mitogenic signaling. We also present evidence that CCND1 plays a role in tumor cell migration. The results provide novel insights for common and differential targets of CCND1 and CCND3 overexpression during pancreatic duct cell carcinogenesis.

Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF.

The firm relies on to build its phones and cellular equipment, including smartphone chips from Qualcomm Inc. and optical components used in base stations from smaller firms such as Maynard, Mass.-based Acacia Communications Inc. The company is now contending with blowback from customers, according to people familiar with the matter. ZTE's coveted U.S. smartphone business is also under threat, with the wireless carrier T-Mobile US Inc. last month telling ZTE it is walking away from an agreement, worth more than a billion dollars, to distribute ZTE smartphones and other gadgets in the U.S., according to people familiar with the matter. The company spent years building its brand there through advertising campaigns and cultivating relationships with wireless carriers.

National-security fears were also behind the U.S. decision in March to of chip maker Qualcomm Inc. by then Singapore-based Broadcom Ltd. on grounds that the deal could endanger American technological prowess. Qualcomm has already been caught in the crossfire, in its effort to acquire Dutch automotive chip maker NXP Semiconductors NV, a purchase the San Diego-based company needs to diversify its product line as the smartphone market plateaus. Huawei has largely been locked out of the U.S. since it and ZTE were the subject of a 2012 House Intelligence Committee report that warned telecom operators not to do business with the companies, saying they posed a national-security threat.

HONG KONG--A North Korea-linked cybercrime ring suspected of raiding Bangladesh's central bank last year was likely responsible for the recent theft of $60 million from a Taiwanese bank, cybersecurity researchers say. In a blog post Tuesday, cybersecurity researchers at U.K. defense company BAE Systems PLC also implicated Lazarus in the Taiwanese theft, saying that tools used in the attack on the Far Eastern International Bank include those used by Lazarus in the past. The breach resulted in the transfer of funds to accounts in Sri Lanka, the U.S. and Cambodia after the perpetrators penetrated the bank's access to the financial-messaging service known as the Society for Worldwide Interbank Financial Telecommunication, or Swift.

HONG KONG--The conglomerate owned by Hong Kong's richest man is selling its fixed-line telecommunications business for $1.86 billion, the latest in series of deals for the sprawling firm. CK Hutchison Holdings Ltd. is selling the telecom business to the New York-based private-equity firm I Squared Capital.

Industrial shares have been pummeled in recent months due to indications of a slowdown in China and uneven growth in the U.S. Shares of Caterpillar rose $1.98, or 2.9%, to $70.88 as the industrial bellwether cut its profit guidance for the year. 3M shares gained 6.18, or 4.1%, to 156 as the company reduced its earnings forecasts for the year and announced 1,500 job cuts.