Complete response to chemotherapy in primary hepatic lymphoma

Primary hepatic lymphoma is an uncommon lymphoid tumor with varied clinical presentations and treatment outcomes. The median age of involvement is 50 years (male preponderance) with median survival as 8-16 months. Here we report a 68-years-old female who presented with right hypochondriac pain and anorexia with hepatomegaly on physical examination. Ultrasonography (USG) with subsequent contrast enhanced computed tomography (CECT) of abdomen depicted a hypoechoic mass in the left lobe of liver. CECT of chest and neck showed no abnormality. Liver biopsy proved to be Non-Hodgkin lymphoma (NHL) diffuse large B cell type, CD20 positive. Bone marrow examination showed no infiltration by NHL. The patient was started on three weekly R-CHOP, given a total of 8 cycles. Patient attained a complete remission documented by negative computed tomography (CT) and positron emission tomography (PET) scans.     

Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers

Numerous cancer therapeutics were originally identified from natural products used in traditional medicine. One such agent is acetyl-11-keto-beta-boswellic acid (AKBA), derived from the gum resin of the Boswellia serrata known as Salai guggal or Indian frankincense. Traditionally, it has been used in Ayurvedic medicine to treat proinflammatory conditions. In this report, we hypothesized that AKBA can affect the growth and metastasis of colorectal cancer (CRC) in orthotopically implanted tumors in nude mice. We found that the oral administration of AKBA (50-200 mg/kg) dose-dependently inhibited the growth of CRC tumors in mice, resulting in decrease in tumor volumes than those seen in vehicle-treated mice without significant decreases in body weight. In addition, we observed that AKBA was highly effective in suppressing ascites and distant metastasis to the liver, lungs and spleen in orthotopically implanted tumors in nude mice. When examined for the mechanism, we found that markers of tumor proliferation index Ki-67 and the microvessel density cluster of differentiation (CD31) were significantly downregulated by AKBA treatment. We also found that AKBA significantly suppressed nuclear factor-κB (NF-κB) activation in the tumor tissue and expression of proinflammatory (cyclooxygenase-2), tumor survival (bcl-2, bcl-xL, inhibitor of apoptosis (IAP-1) and survivin), proliferative (cyclin D1), invasive (intercellular adhesion molecule 1 and matrix metalloproteinase-9) and angiogenic C-X-C (CXC) receptor 4 and vascular endothelial growth factor) biomarkers. When examined for serum and tissue levels of AKBA, a dose-dependent increase in the levels of the drug was detected, indicating its bioavailability. Thus, our findings suggest that this boswellic acid analog can inhibit the growth and metastasis of human CRC in vivo through downregulation of cancer-associated biomarkers.     

The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells — A crucial role for protein kinase C-α inhibition

Listeriosis can lead to potentially lethal pulmonary complications in newborns and immune compromised patients, characterized by extensive permeability edema. Listeriolysin (LLO), the main virulence factor of Listeria monocytogenes, induces a dose-dependent hyperpermeability in monolayers of human lung microvascular endothelial cells in vitro. The permeability increasing activity of LLO, which is accompanied by an increased reactive oxygen species (ROS) generation, RhoA activation and myosin light chain (MLC) phosphorylation, can be completely inhibited by the protein kinase C (PKC) α/β inhibitor GÖ6976, indicating a crucial role for PKC in the induction of barrier dysfunction. The TNF-derived TIP peptide, which mimics the lectin-like domain of the cytokine, blunts LLO-induced hyperpermeability in vitro, upon inhibiting LLO-induced protein kinase C-α activation, ROS generation and MLC phosphorylation and upon restoring the RhoA/Rac 1 balance. These results indicate that the lectin-like domain of TNF has a potential therapeutic value in protecting from LLO-induced pulmonary endothelial hyperpermeability.     

PIG3: A novel link between oxidative stress and DNA damage response in cancer

Reactive oxygen species (ROS), the most prominent free radicals produced in cells, can have both beneficial and detrimental effects on them. Many genes are known to be involved in ROS regulation. P53 inducible gene 3 (PIG3 or TP53I3) was identified in an analysis of genes induced by p53 before the onset of apoptosis. It is a widely conserved gene between many species. Until now it has been shown to exert two disparate cellular roles. The first is that of ROS producer linked to p53 induced apoptosis. In this context, it exhibits a NADPH dependent reductase activity with orthoquinones. The second is that of a component of the DNA damage response pathway. While it is considered as a p53 dependent pro-apoptotic gene, it is rarely affected in cancer. This data does not support an anti-tumor activity. In the present review we present and discuss aspects on the regulation and function of this factor and how it is implicated in cancer. We conclude by proposing that PIG3 may possibly have a role in cancer cell survival.