Given the unlimited proliferation and aerobic glycolysis in tumor cells, these cells require more glucose, glutamine, and other nutrients compared with normal cells. Tumor cells are often affected by insufficient nutrient supply. However, by sensing changes in the nutrient supply in tumor microenvironment and by regulating signal-transduction pathways, some specific proteins can help tumor cells in blocking the cell cycle, reprogramming metabolism, and regulating autophagy to progress and survive against nutri-ent stress. Exciting innovations have been made to elucidate the mechanisms relevant to this process. This review aims to highlight re-cent studies on the mechanisms of sensing the low nutrient supply in microenvironments, as well as the downstream effect factors in cancer cells.

Neovascularization is the fundamental process during tumorigenesis and tumor malignant progression. According the traditional neovascularization theory, tumor vasculatures are mainly developed through angiogenesis by sprouting from preexisting ves-sels and vasculogenesis via recruitment of endothelial progenitor cells from the bone marrow, and the endothelial-dependant vessels are the only way that provides tumor with blood. However, more and more studies indicate that tumor microcirculation network is heteroge-neous and cancer stem cells (CSCs) play an important role during tumor neovascularization. This review highlights the contribution of CSCs to tumor microcirculation modes and the potential anti-angiogenesis targets. Furthermore, this review presents insights for perti-nent studies in the future.

Cellular Fas-associated death domain-like interleukin-1β-converting enzyme inhibitory protein (c-FLIP) belongs to the death effector domain superfamily, which is important in regulating apoptosis and proliferation. c-FLIP inhibits the extrinsic recep-tor-mediated apoptotic pathways and intrinsic mitochondrial apoptotic pathways through competition with caspase-8 for recruitment to Fas-associated death domain protein. Moreover, the cleavage products (i.e., p43-FLIP fragment and p22-FLIP fragment) directly acti-vate NF-κΒ, Erk survival signaling, and other non-apoptotic signaling pathways. The c-FLIP (L) can function either as an anti-apoptotic molecule, in a way analogous to c-FLIP (S) and c-FLIP (R), or as a pro-apoptotic molecule to facilitate the activation of caspase-8 at the death-induced signaling complex. The identified dual functionality of c-FLIP depends on various factors, including its expression level, interaction with caspase-8, and its subcellular localization. c-FLIP is frequently over-expressed in many different tumor types, and con-tributes to tumor cell immune surveillance, chemotherapy resistance, and apoptosis-resistance induced by TNFα, TRAIL, and FasL. Fur-thermore, c-FLIP is essential in obtaining aggressive biological behaviors, and is useful in predicting the prognosis of patients with vari-ous malignant tumors. This review focuses on the molecular mechanisms that control the dual regulation of c-FLIP in life/death deci-sion at death-induced signaling complex. Increasing evidence supports the function of c-FLIP as a tumor therapeutic marker to restore an apoptotic response for TRAIL therapy in cancers. Insight into these processes will improve our understanding of apoptosis, and pro-vide new approaches for rational treatment strategies.

Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Most lncRNAs have pro-nounced oncogenic effects associated with tumorigenesis and progression, promoting the proliferation, migration, invasion, and me-tastasis of tumor cells. The specific lncRNAs expression in particular types of cancers makes them promising diagnostic and prognostic biomarkers. Currently, studies on lncRNAs expression, functions, and mechanisms have attracted considerable attention in cancer re-search. However, these studies mainly focus on epitheliogenic malignant tumors. In this review, we outline the current state of infor-mation on lncRNAs and research progress on its role in haematopoietic and lymphoid tissue tumors.

Ovarian epithelial carcinomas are the most common lethal gynecological malignancies. Ovarian carcinomas are divid-ed into Types I and II based on different morphologies, genetic alterations, and biomarker expression. Low-grade micropapillary serous carcinoma are Type I tumors. Type I tumors are slow growing, generally confined to the ovary at diagnosis, and with better prognosis. These tumors develop from well established precursor lesions that are termedborderlinetumors. Type 1 tumors are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing and highly aggressive neoplasms, for which well defined precursor lesions have not been described. They may arise in the fimbrial epithelium of the oviduct with advanced stage, more aggressive behavior, and worse prognosis. High-grade serous carcino-ma belongs to Type II tumors. This group of tumors has a high level of genetic instability and is characterized by TP53 mutation. Hence, ovarian cancer comprises a heterogeneous group of tumors with distinctly different histological characteristics, molecular genet-ic features, and clinical course.

Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type family, is a broad-spectrum serine proteinase inhibitor. The expression of TFPI-2 is inversely related to increasing degree of malignancy, suggesting a role of TFPI-2 in the mainte-nance of tumor stability and inhibition of the growth of neoplasma. Aberrant methylation of TFPI-2 promoter cytosine-phosphorothio-ate-guanine (CpG) islands has been widely documented to be responsible for diminished expression of TFPI-2 mRNA and protein dur-ing cancer progression. TFPI-2 expression is significantly up-regulated by the ERK1/2 and JNK signaling pathways and modestly in-creased by VEGF, TNF-alpha, and fibroblast growth factor in time-and dose-dependent manners. TFPI-2 can maintain the stability of the tumor environment and inhibit invasiveness and growth of neoplasms. TFPI-2 has also been shown to regulate proliferation, apopto-sis, and vasculogenic mimicry of tumor cells, which may contribute significantly to tumor growth inhibition. Restoration of TFPI-2 ex-pression in tumor tissue inhibits tumor growth and metastasis, which creates a novel possibility of cancer patient treatment. This review focuses on the expression and the molecular regulation mechanisms of TFPI-2 in malignant tumors that control the functions of TFPI-2 in proliferation, apoptosis, and angiogenesis. Insight into these processes will improve our understanding of TFPI-2 and provide new ap-proaches for rational treatment strategies.

Objective: To investigate the relationship of loss of P16 expression with biologlical behaviors and prognosis of gastrointestinal stromal tumors(GISTs). Methods: The expression of P16 protein and mRNA was detected in GISTs tissues by immunohistochemistry,Western blot and RT-PCR.The prognosis was evaluated through follow up. Results: The expression rates of P16 protein and mRNA in GISTs were 53.8%(21/39，Frozen tissue)，51.3%(20/39，Frozen tissues)and 51.4%(37/72，Paraffin-embedded tissues)，respectively.The expression of P16 was significantly different among GISTs of different aggressive risk(P<0.05).With the incease of aggressive risk，the expression of P16 was deceased.The expression of P16 was negtively correlated with Ki-67 and patient survival(P<0.05). Conclusion: The loss of P16 expression has a positive correlation with the infiltration and progression of GIST.Detection of P16 protein and mRNA is helpful for the evalutaion of biological behaviors and prognosis of gastrointestinal stromal tumors.

Objective: To study the expressions of mitochondrial protein (MAB1273), Bcl-2, and Bax in renal cell carcinoma and to investigate their role in the tumorigenesis. Methods: The expressions of mitochondrial protein, Bcl-2 and Bax were detected by immunohistochemistry SP method in 9 tissue samples of renal on-cocytoma, 6 samples of chromophobe carcinoma, 23 samples of clear cell carcinoma and 12 samples of normal renal tissue. Results: The expression of MAB1273 in renal oncocytoma, chromophobe carcinoma and clear cell carcinoma was much higher than that in normal renal tissue (P=0.006). No significant difference was found in MAB1273 expression among the three types of renal carcinoma. The expression of Bcl-2 was higher in the renal carcinoma groups than in the normal renal tissue group, with a significant difference (P=0.008). The expression of Bax was not different among all of the groups (P=0.057). Rank correlation analysis showed a positive correlation between MAB1273 and Bcl-2 expression (r=0.341, P=0.015). The expression of Bcl-2 was negatively correlated with Bax expression (r= -0.287, P=0.043). Conclusion: Overexpression of mitochondrial protein and Bcl-2 and underexpression of Bax may play a part in the genesis of renal oncocytoma, chromophobe carcinoma and the clear cell carcinoma, indicating that overexpression of MAB1273 may be correlated with apoptosis of renal cell carcinoma cells.

Objective:The clinicopathological features, diagnosis, and prognosis of follicular thyroid carcinoma (FTC) with distant me-tastasis as the first manifestation were evaluated in this study. Methods:A total of 129 FTC cases with clinical data were retrospective-ly analyzed in the Department of Pathology, Tianjin Medical University Cancer Institute and Hospital (January 2001 to January 2016). Survival analysis and conjoint analysis on FTC with clinical data, diagnosis, and morphological characteristics with distant metastasis as the first manifestation were performed. Results:Among the 129 FTC cases, 24 cases demonstrated distant metastasis as the first mani-festation (18.6%). Bone metastasis was the most common (13.2%). The presence of mass and pain at the metastatic sites were the usu-al clinical complaints. The morphological characteristics of FTC with distant metastasis can be classified into four subtypes:microfollicu-lar (10 cases), solid (4 cases), normofollicular (9 cases), and macrofollicular (1 case). Immunostaining tests on thyroglobulin and thyroid transcription factor-1 showed positive results in FTC with metastasis. Survival analysis showed that the five-year survival rates in the 24 cases were 87.1%. The prognosis of patients with solitary metastasis was better than that of patients with multiple metastasis (P=0.022). A higher survival rate was found in the normofollicular and macrofollicular subtypes than that detected in the microfollicular and solid subtypes (P=0.012). Conclusion:FTC is susceptible to distant metastasis. Some patients with FTC demonstrated distant me-tastasis as the first manifestation, and their diagnosis can be confirmed by pathological feature analysis and immunostaining. The prog-nostic significance is possibly related to the number of lesions of FTC with distant metastasis and histopathological subtypes.

Objective:To investigate the inhibitory effect of Dickkopf-1 (Dkk1) on vasculogenic mimicry (VM) formation and the relevant mechanism. Methods:CD34-PAS dual staining and immunohistochemical staining were used to detect and analyze the re-lationship between VM existence and Dkk1 expression in 217 human colon cancer tissue samples;three dimensional (3D) culture was used to detect the influence of Dkk1 on tube structure formation and on VE-cadherin expression;a subcutaneous mouse xenograft mod-el was made to further validate the inhibitory role of Dkk1 on VM formation in vivo. Results:VM-positive samples indicated a lower expression of Dkk1(P<0.05);colon cancer cells with Dkk1 overexpression exhibited a decreased ability to form tube-like structure and a decreased expression of VE-cadherin;Dkk1 inhibited the VM-formation abilities of human colorectal carcinoma cell line xenograft tu-mor tissue. Conclusion:Dkk1 inhibits the VM formation of colon cancer.