Legumes belonging to Fabaceae family of the order Fabales are a rich and important source of proteins and many essential elements. Due to its nutritious elements, these are preferably included in human diet in most part of the world. But, unfortunately, IgE binding proteins have been identified in majority of legumes, and allergenic response to these legumes may range from mild skin reactions to life-threatening anaphylactic reaction. Overall, allergenicity due to consumption of legumes in decreasing order may be peanut, soybean, lentil, chickpea, pea, mung bean, and red gram. So far, several allergens from different legumes have been identified and characterized. Most of identified allergens belong to storage proteins family, profilins, or the pathogenesis-related proteins. Legumes also have property of immunological cross-reactivity among themselves and from other sources that also increases the severity of allergenic response to a particular legume. This review summarizes the currently available knowledge on legume allergy and describes the allergenic problems associated with different legumes. It also tries to explore about the legume allergens identified so far by different scientific groups. The culmination of knowledge about identification and characterization of allergens from different legumes will be helpful in diagnosis and treatment of allergy, for development of novel therapeutic strategies, for strict avoidance of particular legume in diet by susceptible individual and also to produce hypoallergenic cultivars of leguminous crop through conventional breeding or genetic modification.

Pdx1-Cre x LSL-Kras G12D x LSL-TP53 R172H (KPC), Pdx1-Cre x LSL-Kras G12D x LSL-TP53 R172H+/+ (KPPC), Gemcitabine resistant (GR), Anti-PD-1 (αPD-1).

Pancreatic ductal adenocarcinoma (PDAC) remains remarkably lethal with a 5-year survival rate of 8%. This is mainly attributed to the late stage of presentation, as well as widespread resistance to conventional therapy. In addition, PDAC tumors are largely nonimmunogenic, and most patients have displayed incomplete responses to cancer immunotherapies. Our group has previously identified TGFb as a crucial repressor of antitumor immune function in PDAC, particularly with respect to cytotoxic T lymphocytes. However, pharmacologic inhibition of TGFb signaling has had limited efficacy in clinical trials, failing to promote a significant antitumor immune response. Hence, in this work, we extend our analysis to identify and circumvent the mechanisms of resistance to TGFb signal inhibition in PDAC. Consistent with our previous observations, adoptive transfer of TGFb-insensitive CD8 þ T cells led to the near complete regression of neoplastic disease in vivo. However, we demonstrate that this cannot be recapitulated via global reduction in TGFb signaling, through either genetic ablation or pharmacologic inhibition of TGFBR1. In fact, tumors with TGFb signal inhibition displayed increased PD-L1 expression and had no observable change in antitumor immunity. Using genetic models of advanced PDAC, we then determined that concomitant inhibition of both TGFb and PD-L1 receptors led to a reduction in the neoplastic phenotype, improving survival and reducing disease-associated morbidity in vivo. Combined, these data strongly suggest that TGFb and PD-L1 pathway inhibitors may synergize in PDAC, and this approach warrants clinical consideration. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.

Abrogation of endoplasmic reticulum (ER) protein folding triggered by exogenous or endogenous factors, stimulates a cellular stress response, termed ER stress. ER stress reestablishes ER homeostasis through integrated signaling termed the ER-unfolded protein response (UPRER). In the presence of severe toxic or prolonged ER stress, the pro-survival function of UPRER is transformed into a lethal signal transmitted to and executed through mitochondria. Mitochondria are key for both apoptotic and autophagic cell death. Thus ER is vital in sensing and coordinating stress pathways to maintain overall physiological homeostasis. However, this function is deregulated in cancer, resulting in resistance to apoptosis induction in response to various stressors including therapeutic agents. Here we review the connections between ER stress and mitochondrial apoptosis, describing potential cancer therapeutic targets.