Adjuvant therapy of pancreatic cancer using monoclonal antibodies and immune response modifiers

Summary: Pancreatic cancer is a devastating disease with poor survival. At present, no effective adjuvant or palliative therapies are available. Unresponsiveness to chemotherapy, radiotherapy, and antihormonal treatment is one of the reasons that pancreatic cancer patients have an overall median survival time of 4-6 mo. This article summarizes clinical trials on immunotherapy of pancreatic cancer using the murine monoclonal antibodies (MAbs) 17-1A and BW 494. In addition, the use of MAb treatment in combination with immune response modifiers is discussed. In four clinical trials, MAb 17-1A was given by iv infusion to 100 patients with pancreatic cancer. In 30 of these patients, antibody treatment was accompanied, by γ-interferon, also given intravenously. Complete response, partial response, and stable disease were reported in 1, 5, and 23 patients, respectively. Passive immunotherapy using the MAb BW 494 was carried out in 148 pancreatic cancer patients in two phase I and two phase II trials. In 1 out of 75 patients a partial response and in 25 out of 74 paitents stable disease were reported. However, in a controlled, randomized trial enrolling, 61 patients following Whipple resection, comparable survival times in patients with, and without MAb BW 494 treatment led to the termination of further clinical trials with this antibody. New clinical studies using humanized MAbs in combination with immune response modifiers should be initiated to, further evaluate immunotherapy as a treatment option in pancreatic cance

Cancer cachexia

In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome

Nerve-Cancer Interactions in the Stromal Biology of Pancreatic Cancer

Interaction of cancer cells with diverse cell types in the tumor stroma is today recognized to have a fate-determining role for the progression and outcome of human cancers. Despite the well-described interactions of cancer cells with several stromal components, i.e., inflammatory cells, cancer-associated fibroblasts, endothelial cells, and pericytes, the investigation of their peculiar relationship with neural cells is still at its first footsteps. Pancreatic cancer (PCa) with its abundant stroma represents one of the best-studied examples of a malignant tumor with a mutually trophic interaction between cancer cells and the intratumoral nerves embedded in the desmoplastic stroma. Nerves in PCa are a rich source of neurotrophic factors like nerve growth factor (NGF), glial-cell-derived neurotrophic factor (GDNF), artemin; of neuronal chemokines like fractalkine; and of autonomic neurotransmitters like norepinephrine which can all enhance the invasiveness of PCa cells via matrix-metalloproteinase (MMP) upregulation, trigger neural invasion (NI), and activate pro-survival signaling pathways. Similarly, PCa cells themselves provide intrapancreatic nerves with abundant trophic agents which entail a remarkable neuroplasticity, leading to emergence of more routes for NI and cancer spread, to augmented local neuro-surveillance, neural sensitization, and neuropathic pain. The strong correlation of NI with PCa-associated desmoplasia suggests the potential presence of a triangular relationship between nerves, PCa cells, and other stromal partners like myofibroblasts and pancreatic stellate cells which generate tumor desmoplasia. Hence, although not a classical hallmark of human cancers, nerve-cancer interactions can be considered as an indispensable sub-class of cancer-stroma interactions in PCa. The present article provides an overview of the so far known nerve-cancer interactions in PCa and illustrates their ominous role in the stromal biology of human PCa

The Role of PPARγ Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPARγ pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPARγ agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPARγ

Complications of pancreatic surgery

AbstractPancreatic resection is the only treatment option that can lead to a meaningful prolonged survival in pancreatic cancer and, in some instances, perhaps a potential chance for cure. With the advent of organ and function preserving procedures, its use in the treatment of chronic pancreatitis and other less common benign diseases of the pancreas is increasing. Furthermore, over the past two decades, with technical advances and centralization of care, pancreatic surgery has evolved into a safe procedure with mortality rates of <5%. However, postoperative morbidity rates are still substantial. This article reviews the more common procedure‐related complications, their prevention and their treatment

B7-H3 and Its Role in Antitumor Immunity

B7-H3 is one of the most recently identified members of the B7/CD28 superfamily of costimulatory molecules serving as an accessory modulator of T-cell response. Recently, B7-H3 expression has been reported in several human cancers indicating an additional function of B7-H3 as a regulator of antitumor immunity. However, its precise physiologic role is still elusive, because both stimulatory and inhibitory capacities have been demonstrated. This paper summarizes the available data on B7-H3 in the regulation of T-cell response focusing on its potential role in antitumor immunity