Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have been successful in restoring sensitivity to the primary chemotherapy (gemcitabine) and enter the clinical treatment arena.

Methods: We examined the ability of cellular arginine depletion through treatment with PEG-ADI to alter in vitro and in vivo cytotoxicity of gemcitabine.

Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma.

Background: Isolated limb infusion (ILI) with melphalan is a minimally invasive, effective treatment for in transit melanoma. We hypothesized that burden of disease (BOD) would correlate to treatment response.

Methods: We retrospectively analyzed a prospectively collected database from two academic centers.

Role of autophagy in apoptotic regulation by Akt in pancreatic cancer.

Background/aim: The Akt signaling pathway mediates a potent anti-apoptotic signal in pancreatic cancer and inhibition of this pathway has become an attractive mechanism to increase the efficacy of traditional chemotherapies. Autophagy is a lysosomal catabolic pathway by which eukaryotic cells recycle macromolecules and organelles. Although autophagy may function as a survival mechanism under metabolic stress conditions, it also serves as an alternate route to programmed cell death distinct from apoptosis.

The role of Akt activation in the response to chemotherapy in pancreatic cancer.

Unlabelled: The PI3K/Akt signaling pathway is constitutively activated in some pancreatic cancers; when activated, it inhibits chemotherapy-mediated apoptosis. We examined whether Akt activity correlates with apoptotic resistance to chemotherapy in pancreatic cancer.

Materials And Methods: A panel of human pancreatic cancer cells was evaluated for basal Akt activity as well as response to three chemotherapies.

Targeting Bcl-2-mediated cell death as a novel therapy in pancreatic cancer.

Background: Bcl-2 is an essential regulator of programmed cell death (PCD). Overexpression of Bcl-2 is common in pancreatic cancer; the high levels have been shown to correlate with resistance to PCD. This resistance is mediated by binding of Bcl-2 via its BH-3 domain to diverse proteins, including the Bax/Bak family members, various protein kinases, and beclin 1, which are involved in regulation of autophagy (type II PCD).

Surgery in the patient with liver disease.

Liver dysfunction is a prominent entity in Western medicine that has historically affected patients suffering from chronic viral or alcoholic hepatitis. The incidence of these conditions has not changed dramatically in recent years but the overall number of patients with liver dysfunction has increased considerably with the emergence of the obesity epidemic. Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as the most common cause of chronic liver disease in the United States.

Surgery in the patient with liver disease.

Liver dysfunction is a prominent entity in Western medicine that has historically affected patients suffering from chronic viral or alcoholic hepatitis. The incidence of these conditions has not changed dramatically in recent years but the overall number of patients with liver dysfunction has increased considerably with the emergence of the obesity epidemic. Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as the most common cause of chronic liver disease in the United States.

Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase.

Human alpha-chymase is an efficient angiotensin (AT) converting enzyme, selectively hydrolyzing AT I at Phe8 to generate bioactive AT II, which can promote cardiac hypertrophy, vascular stenosis, and hypertension. Some related enzymes, such as rat beta-chymase 1, are much less selective, destroying AT by cleaving at Tyr4. Comparisons of chymase structure and activity led to speculation that interaction between AT and the side chain of Lys40 or Arg143 accounts for the human enzyme's marked preference for Phe8 over Tyr4.