The question of whether trade affects conflict is important for public policy. To date, theoretical studies have treated trade or the gains from trade as exogenous. However, a dyad's gains from trade are influenced by a number of factors, including foreign aid, tariffs, contiguity, and relative country size. This article presents a mathematical model to extend the conflict-trade model to incorporate foreign aid, tariffs, contiguity, and country size. In particular, we examine how the gains from trade are affected by these factors, with foreign aid, and contiguity increasing the gains from trade and tariffs reducing the gains from trade. Small countries have larger trade gains when trading with a large country than with a small country. If countries seek to protect their trade gains, the model predicts that foreign aid and contiguity will decrease conflict, while tariffs will increase conflict. The contiguity result suggests that conflict between neighboring countries would be greater than observed if not for the mitigating effects of trade. Trade with large countries decreases conflict more than trade with small countries. In addition, rather than concentrating solely on bilateral interactions, the models are specified in enough detail to garner implications concerning the effects of changes in the terms of trade on third parties. Empirical results, generally supporting the hypotheses, are presented using a sample from the Conflict and Peace Data Bank.

Obesity has been recognized as a risk factor for breast cancer. Adipocyte-derived leptin may play as a paracrine regulator on the growth of breast cancer cells. Expression of both leptin and its OB-Rb receptor was detected in human breast cancer ZR-75-1 cells and further induced by leptin, suggesting that both expression and message mediation of leptin were autoregulated by itself. With cell counting and MTT assay, we had observed leptin stimulated ZR-75-1 growth in dose- and time-dependent manners. To study what steps of cell cycle progression leptin may involve in, we analyzed cell-cycle profile with flow cytometric analysis, mRNA and protein expressions of four cell-cycle regulators with RT-PCR and Western blotting analysis. Under the treatment of leptin, the G1 arrest of cells was reduced accompanied with up-regulation of G1 phase-specific cyclin D1 and proto-oncogene c-Myc, but down-regulation of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and tumor suppressor p53. Furthermore, JAK2 inhibitor AG490, PI3K/Akt inhibitor Wortmannin, and MEK/ERK1/2 inhibitor PD98059 were efficiently prevented leptin-promoted cell growth. Effect of cooperation between leptin and estrogen on ZR-75-1 growth had been observed. Collectively, the results showed that the proliferative effect of leptin on ZR-75-1 was associated with the up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21(WAF1/CIP1) plausibly through a hypothesized JAK2-PI3K/Akt-MEK/ERK pathway. The leptin- and OB-Rb-expressing capability of ZR-75-1 created a possible autocrine control of leptin, in which signal could be effectively amplified by itself, on cell growth.

Breast-conserving surgery with clear margins is the current treatment of choice for phyllodes tumors, but this strategy does not further reduce local recurrence effectively. Optimal management continues to be a challenge.

Obesity is known to be an important risk factor for many types of cancer, such as breast, prostate, liver and endometrial cancer. Recently, epidemiological studies have indicated that obesity correlates with an increased risk of developing ovarian cancer, the most lethal gynecological cancer in developed countries. Leptin is predominantly produced by adipocytes and acts as a growth factor and serum leptin levels positively correlate with the amount of body fat. In this study, we investigated the effects of leptin on the growth of ovarian cancer cells and the underlying mechanism(s) of action. Our results showed that leptin stimulated the growth of the OVCAR-3 ovarian cancer cell line using MTT assay and trypan blue exclusion. Using western blot analysis, we found that leptin enhanced the expression of cyclin D1 and Mcl-1, which are important regulators of cell proliferation and the inhibition of apoptosis. To investigate the signaling pathways that mediate the effects of leptin, cells were treated with leptin plus specific inhibitors of JAK2, PI3K/Akt and MEK/ERK1/2 and analysis of the phosphorylation state of proteins was carried out by western blot assays. We showed that the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways were involved in the growth-stimulating effect of leptin on ovarian cancer cell growth and the specific inhibitors of PI3K/Akt and MEK/ERK1/2 revealed that these two pathways interacted with each other. Our data demonstrate that leptin upregulates the expression of cyclin D1 and Mcl-1 to stimulate cell growth by activating the PI3K/Akt and MEK/ERK1/2 pathways in ovarian cancer.

Obesity serves as an important risk factor for incidences of both cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC), which is the third leading cause of cancer death worldwide. Leptin, the obesity biomarker molecule secreted systemically by body fat mass and locally by activated hepatic stellate cells, is proposed to play a certain role in HCC growth. Here, we show both proliferative and anti-apoptotic effects of leptin in HCC cells. Leptin stimulated cyclin D1 promoter activity to increase cyclin D1 protein expression, which accelerated the cell cycle progression. The reduced ratio between anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) Bcl-2 family proteins by transforming growth factor (TGF)-b1 caused HCC cells degradation of poly(ADPribose) polymerase and consequential apoptosis; whereas, leptin protected cells from apoptosis by reversing TGF-b1-reduced Bcl-2/Bax ratio as a result of down-regulating Bax. Any inhibitor specific for Janus kinase 2 (JAK2), phosphatidylinositol 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase 1/2 (ERK1/2) blocked these leptin functions. When intrahepatocytic JAK2 was activated by leptin, the active JAK2 afterward triggered a signaling cascade involving activations of PI3K/Akt and MEK/ERK1/2 in order of occurrence. As yet, in most cases, the crosstalks among signaling pathways primarily studied in diverse cancer cell types for mediating somatotropic effect of leptin are not well clarified and seem to be cell-type dependent. For the first time, our results demonstrate the direct effects of leptin on HCC growth and define its signal pathway with a crosstalking JAK2-PI3K/Akt-MEK/ERK1/2 connection. The identified hierarchy of intrahepatocytic leptin signaling pathway provides a clear basis potentially beneficial to make accurate and effectual strategies for facing both cirrhotic and non-cirrhotic liver carcinogenesis.

Aims: We investigated the relationship between serum leptin concentrations and polymorphism of the leptin receptor gene and breast cancer. Methods: Serum leptin concentrations were measured by enzyme-linked immunosorbent assay in 47 women with invasive breast cancer compared with 41 age-matched controls without cancer. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the leptin receptor gene at codon 109 (LEPR-109) was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Patients with breast cancer had a higher mean serum leptin concentration than women in the control group, but the difference was not statistically significant. Among those with breast cancer, the serum leptin concentration was higher in women with high-grade cancers (p = 0.020). The LEPR-109RR genotype was more frequent in premenopausal patients with tumors larger than 2 cm (p = 0.039) and in premenopausal women who were overweight (p = 0.029). Among patients with the LEPR-109RR genotype, higher mean serum leptin concentrations were present in those with triple-negative cancers (p = 0.048). Conclusions: Our study suggests an association between serum leptin concentration and tumor progression. LEPR-109 polymorphism in premenopausal women appears to be associated with obesity and tumor progression.

The results indicate no significant benefits of intravenous lidocaine infusion in terms of acute postoperative pain. Although lidocaine seems to attenuate the risk of chronic pain after breast surgery, there is insufficient evidence to conclude that lidocaine infusion is of proved benefit because the results were based on a limited number of small trials.

Leptin interferes with ACTH/cAMP signaling, possibly through a cAMP-degrading mechanism involving activation of JAK2, phosphatidylinositol 3-kinase, and PDE3, to down-regulate P450scc expression and consequent adrenal steroidogenesis.