Nonspecific immunotherapy Innate Immune system and cytokine

Nature kill cells are the central component of the innate immunity and play an important role in cancer immunosurveilance. It has been reported that NK cells can recognize and control tumor growth by direct cellular cytotoxicity and secrete immunostimulatory cytokines such as IFN-y. The further researches have demonstrated NK cells can eliminate tumor cell by inhibiting cellular proliferation, angiogenesis, promoting apoptosis and stimulate the adaptive immune system. In mouse experimental...

Adoptive cell transfer

In cellular antitumor immunity, T-cells must first be activated by bone marrow derived APCs that present tumor antigens and provide essential co-stimulatory signals, migrate and gain access to the tumor microenvironment, and overcome obstacles to effective triggering posed by the tumor. Dendritic cells, which are the strongest antigen presenting cells in the body. Their generation for anti-tumor immunity has been the focus of a vast array of scientific and clinical studies. DC's specialized...

Transforming growth factorp Tgfp Smad4 MET and IGF1

TGF-P binds to cell receptors that lead to downstream activation of SMAD4 which in turn moves into the cell nucleus to activate gene transcription. TGF-P is also involved with activating other pathways including Ras, PI3K and MAPK. Although tumour suppressive in epithelial cells, it is also involved in mediating invasion and metastasis. In pancreatic cancer, mutations in SMAD4 are seen in 50 and up to 4 of TGFp receptors. 91 Mutations of the former can lead to reduced TGF-P tumour suppression...

Active immunotherapy

Vaccine The development of human therapeutic cancer vaccines has come a long way since the discovery of major histocompatability complex (MHC) restricted tumor antigens. As an new method to reconsituting immunity, cancer vaccionation can actively harness the intrinsic power of the immne system to recognize and destroy tumors. The ideal designed vaccine should actively generate antigen-specific immune response to abnomal protein expressed in tumor cells, including activating distinct components...

References

Molecular weight-dependent influence of heparin on the form of tissue factor pathway inhibitor circulating in plasma. Semin Thromb Hemost. Vol.27, pp. 503-511. ISSN 0094-6176. Altinbas, M. Coskun, H.S. Er, O. Ozkan, M. Eser, B. Unal, A., et al. (2004). A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost, vol.2, pp. 1266-1271, ISSN 15387933. Ay, C. Simonek, R. Vormittag, R., et al....

Introduction

Pancreatic cancer (PCa) as one of the most aggressive malignancies of mankind has an unparallelled propensity to invade intrapancreatic nerves. This neural invasion is therefore one of the most frequent routes of spread in PCa in addition to lymphatic and vascular paths. The major clinical relevance of neural invasion (NI) has triggered intense research efforts to understand its pathomechanims, and the findings derived from all these studies show how multi-faceted this peculiar route of cancer...

Patient with jaundice

Jaundice results from an abnormally high bilirubin in the blood whose origin may be difficulty in eliminating it's then an obstructive jaundice. This is the most symptom in patients with periampullary cancer (located near the Vater's ampulla) or cancer of the pancreatic head. It can be considered a risk factor for postoperative complications. 8, 9 Many studies demonstrate that it could be associated with a higher incidence of insufficient postoperative renal function, but also of sepsis,...

Biomarkers in pancreatic cancer

In contrast to other solid tumour malignancies, there have been relatively modest or poor responses achieved with molecularly targeted agents to date in unselected patients with pancreatic cancer. There is an urgent need for a personalised approach to better define biomarkers in order to predict patients that are more likely to benefit from a particular cytotoxic or molecular targeted therapy. The biomarker with the most preclinical and clinical evidence is human equilibrative nucleoside...

Diabetes

Nearly 80 of PC patients have either frank diabetes or impaired glucose tolerance. Diabetes is usually diagnosed either concomitantly or during the two years preceding the diagnosis (Gullo et al. 1994 Permet et al. 1993). The link between abnormal glucose and PC exists only for type II diabetes. Better glycaemic control in diabetic patients undergoing major surgery has been shown to improve perioperative mortality and morbidity. Diabetics are at increased risk of myocardial ischaemia,...

Diagnosis of pancreatic neoplasia

Currently, imaging modalities for detection of pancreatic masses include ultrasonography (US), computed tomography (CT) scan, magnetic resonance imaging (MRI) magnetic resonance cholangiopancreatography, endoscopic ultrasonography (EUS). In clinical practice differential diagnosis of pancreatic masses is frequently a clinical challenge often therapeutic decision in this context is mainly based on the ability to perform a diagnosis of malignancy or to exclude malignancy (Tamm & Charnsangavej,...

Pain and inoperable pancreatic cancer

Pancreatic diseases such as cancer can cause clinically significant pain in the upper abdomen, which may radiate to the back. Pain management for pancreatic cancer patients is one of the most important aspects of their care, as it is one of the most weakening symptoms. The best therapy involves adequate therapy with constant assessment. The current management of pancreatic pain follows the WHO three-step ladder for pain control, starting with non-opioid analgesics such as nonsteroidal...

Summary and conclusion

Neural invasion in PCa bears a unique importance in the biology of this disease due its impact on patient survival, local tumor reccurence and neuropathic pain sensation. Higher interest in NI has paved path for increased research on the biology of NI and accelarated the development of numerous experimental models. The discussed in vitro and in vivo models which shall help to eludicate the pathomechanisms of NI in PCa may provide novel tools to control and to reduce NI in this highly aggressive...

Vaccines against pancreatic tumour antigens

To develop the ideal vaccine for pancreatic cancer, the following wish list would probably need to be fulfilled. First, specific cell-surface proteins must be identified that are that are crucial in the cancer growth or progression pathway and are unique to pancreatic cancer tumours. Second, these tumour-exclusive proteins should be shown to elicit a vigorous tumour-protein-specific immune response. Third, the best carrier to deliver the appropriate immunogenic tumour proteins should be...

Epidural anaesthesia analgesia

The epidural space is surrounded by the outer surface of the dura mater and the bony and ligamentous walls of the spinal canal and extends from the foramen magnum to the sacral hiatus. The cross-sectional area of the epidural space becomes smaller cranially, as the theca and its contents tend to occupy a greater proportion of space. Hence, a given volume of drugs affects a greater number of segments the more cranially it is introduced. The epidural space contains nerve roots, fat, spinal...

Why are pancreatic cancer cells attracted to nerves Molecular mechanisms of neural invasion in PCa

Neural Control Lymph Vessels

Researchers and clinicians have long puzzled about why PCa cells are frequently encountered around intrapancreatic nerves. Early reports had claimed that PCa cells enter nerves through the perineurium at its weakest points, i.e. along neural lymph vessels(di Mola& di Sebastiano, 2008), which, however, could not be confirmed in later studies. In later studies, investigators suggested that PCa cells grow along the path of least resistance after entering nerves, which was thought to be the...