lactoferrin and Pancreatic-Neoplasms

Lactoferrin (LF)--in various quantities--is present in human milk, secretions and polymorphonuclear neutrophils (PMN). LF's significance lies in its bacteriostatic effect on its environment. Probably it prevents bacterial uptake of iron, leads to damage of bacteria and during phagocytosis helps the organism to combat pathogens. Most likely it regulates iron absorption, and during inflammation it takes part in the plasma iron transport. LF is believed to play an important role in the regulation of granulopoiesis in the bone-marrow. From its biological effects it appears that plasma LF determinations may be useful in the clinical diagnosis of leukaemia and other malignant diseases, as well as in the study of iron metabolism.

Topics: Absorption; Animals; Biological Transport; Cell Division; Chronic Disease; Granulocytes; Humans; Inflammation; Iron; Kinetics; Lactoferrin; Lactoglobulins; Leukemia, Myeloid; Milk; Pancreatic Neoplasms; Pancreatitis

Topics: Biopsy; Carcinoembryonic Antigen; Celiac Artery; Cholangiography; Cholecystokinin; Lactoferrin; Laparoscopy; Mesenteric Arteries; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Radionuclide Imaging; Secretin; Tomography, X-Ray Computed; Ultrasonography

Amyloid deposition in pancreas is rare. Lactoferrin amyloid deposition has not been reported in pancreas, till date. Presence of enhancing mural nodule in a cyst on imaging is a worrisome feature for malignancy, and warrants surgical resection in a surgically fit candidate, as per Fukuoka guidelines for management of cystic lesions in pancreas.. We report a case of localized amyloidosis presenting as a mural nodule in a 1.6 cm cyst located in the head of pancreas, which led to pancreatoduodenectomy in a 69 year old woman. Histological evaluation revealed a simple mucinous cyst with localized lactoferrin amyloid deposition corresponding to the mural nodule identified on imaging.. We report the first case of localized lactoferrin amyloid deposition in pancreas that presented as a mural nodule in a cystic lesion and prompted pancreatoduodenectomy. This unique case illustrates that on rare occasion mural nodule in a cyst can be benign. It adds amyloid deposition to the differential diagnosis of mural nodules in pancreatic cystic lesions seen on imaging.

Topics: Aged; Amyloidosis; Female; Humans; Lactoferrin; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Pancreaticoduodenectomy

Quinacrine is an antimalarial drug that was repositioned for treatment of cancer. This is the first work to enhance quinacrine activity and minimize its associated hepatotoxicity via loading into bio-degradable, bio-renewable lignosulfonate nanoparticles. Particles were appraised for treatment of pancreatic cancer, one of the most life-threatening tumors with a five-year survival estimate. Optimum nanocomposites prepared by polyelectrolyte interaction exhibited a particle size of 138 nm, a negative surface charge (-28 mV) and a pH dependent release of the drug in an acidic environment. Ligands used for active targeting (lactoferrin and hyaluronic acid) were added to nanoparticles' surface via layer by layer coating technique. The highest anticancer activity on PANC-1 cells was demonstrated with dual active targeted particles (3-fold decrease in IC

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Movement; Cell Survival; Delayed-Action Preparations; Drug Liberation; Erythrocytes; Humans; Hyaluronic Acid; Lactoferrin; Lignin; Male; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Pancreatic Neoplasms; Quinacrine; Rabbits

The ubiquitin-proteasome system (UPS) is composed of E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme, and E3 ubiquitin ligase, which play a fundamental role in mediating intracellular protein degradation. Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. However, the key pathway for UPS to promote ferroptotic cell death is still poorly understood. Here, we screened 571 UPS-related E1, E2, and E3 genes in a human pancreatic cancer cell line (PANC1) and identified the upregulation of NEDD4-like E3 ubiquitin protein ligase (NEDD4L) as a novel ferroptosis suppressor. Mass spectrometry analysis further showed that lactotransferrin (LTF), an iron-binding transport protein, is a direct NEDD4L-binding protein. Consequently, NEDD4L-mediated LTF protein degradation inhibits intracellular iron accumulation and subsequent oxidative damage-mediated ferroptotic cell death in various cancer cells. These findings establish a new molecular link between UPS and ferroptosis, which may lead to the development of potential anticancer strategies.

Topics: Cell Line, Tumor; Ferroptosis; Gene Expression Regulation, Neoplastic; Humans; Iron; Lactoferrin; Nedd4 Ubiquitin Protein Ligases; Pancreatic Neoplasms; Proteolysis; Reactive Oxygen Species

Pancreatic cancer is one of the most lethal cancers, with an incidence equaling mortality. It is a heterogeneous group of neoplasms in which pancreatic ductal adenocarcinoma is most common. Pancreatic cancer cannot be cured even if detected early. When treatment is initiated, a suitable method of administration of anticancer drugs must be chosen. Anticancer drugs kill tumor cells. However, side effects including initiation are problematic in anticancer drug therapy. Improved methods for the diagnosis of side effects of pancreatic cancer by using sensitive and specific tumor markers are highly desirable. Therefore, efficient strategies for biomarker discovery are urgently needed. Here, we present an approach based on direct experimental access to proteins released by PANC-1 human pancreatic cancer cells in vitro. A two-dimensional (2-D) map and catalog of this subproteome, herein termed the secretome, were established comprising more than 1,000 proteins observed by '2-D difference in-gel electrophoresis analysis using cyanine dye'. We investigated 22 spots that were 1.20-fold upregulated and 31 spots that were 0.66-fold downregulated by gemcitabine chloride treatment. Proteins in these spots were identified by nano-high-performance liquid chromatography electrospray ionization time of flight mass spectrometry/mass spectrometry. Most secretome constituents were nominally cellular proteins. By mass spectrometry screening, 14-3-3 protein sigma (14-3-3 σ), protein S100-A8, protein S100-A9, galectin-7, lactotransferrin (lactoferrin, LF) precursor, serotransferrin (transferrin) precursor, and vitamin D binding protein precursor were identified. Western blotting confirmed the presence of 14-3-3 σ and LF. We found that upregulation of 14-3-3 σ was associated with apoptosis, and downregulation of LF was found to suppress tumorigenesis.

Topics: 14-3-3 Proteins; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Deoxycytidine; Gemcitabine; Humans; Lactoferrin; Neoplasm Proteins; Pancreatic Neoplasms; Proteomics; S100 Proteins; Transferrin

A well characterized, peptide derivative of bovine lactoferrin, L12, has been shown to possess anticancer properties in multiple cell lines. However, adverse side effects in normal tissues and poor plasma kinetics that hinder the clinical effectiveness of current chemotherapeutics also deter the potential for effective delivery of this L12 peptide. To overcome these limitations, we have developed an Elastin-like polypeptide (ELP) carrier that has the potential to thermally target therapeutic peptides and chemotherapeutics to a tumor site. The coding sequence of ELP was modified with the L12 peptide at the C-terminus and a membrane transduction domain derived from the HIV-1 Tat protein at the N-terminus (Tat-ELP-L12). The thermally responsive Tat-ELP1-L12 is soluble in aqueous solutions at 37 degrees C but aggregates near 41 degrees C, which makes Tat-ELP1-L12 ideal for targeting to solid tumors on application of focused hyperthermia. We observed that under hyperthermia conditions at 42 degrees C, Tat-ELP1-L12 mediated cytotoxicity in MIA PaCa-2 pancreatic adenocarcinoma cells was enhanced by nearly thirty-fold. We investigated the mechanisms of cell death and found evidence of mitochondrial membrane depolarization and caspase activation, which are characteristic of apoptosis, as well as, increased membrane permeability, as shown by LDH release. These results suggest that Tat-ELP1-L12 possesses cytotoxic properties to cancer cells in vitro and may have the potential to provide an effective vehicle to thermally target solid tumors.

Topics: Animals; Antineoplastic Agents; Cattle; Cell Line, Tumor; Cell Proliferation; Drug Carriers; Hemolysis; Humans; L-Lactate Dehydrogenase; Lactoferrin; Membrane Potential, Mitochondrial; Pancreatic Neoplasms; Peptides; Rats; Temperature

This paper describes the antitumor effect of human lactoferrin against the human pancreatic cancer cell line SPA, which was newly established in our laboratory from a metastatic liver tumor of pancreatic origin. In tissue culture, the cancer cells proliferated rapidly at 16 hours of doubling time, and produced tumor markers into the culture medium at a high concentration. Subcutaneous and intraperitoneal transplantation of these neoplastic cells into nude mice resulted in tumor formation and carcinomatous peritonitis. The inhibitory effect of human lactoferrin on the cell growth of SPA was found both in vivo and in vitro. There was significant inhibition of cell growth in vivo at the concentration of 1 microgram/ml of hLf in the culture medium. And in the in vivo assay, hLf delayed the growth of subcutaneously transplanted tumors into BALB/c nude mice, and the effect was retained for two weeks. These results indicate the possibility that hLf will become one of the new drugs for adjuvant therapy against pancreatic cancer.

Topics: Animals; Antineoplastic Agents; Cell Division; Humans; Lactoferrin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Tumor Cells, Cultured

The immunohistochemical detection of lactoferrin was carried out with the PAP technique on pancreatic tissue samples of 23 patients, operated for acute (13) or chronic (4) pancreatitis as well as for adenocarcinomas (6). In order to control our immunohistochemical technique and the antisera produced by us we studied some tissue samples of human mammary gland and parotis. We detected lactoferrin in the glands of parotis and mammae as well as of their secretions. In the pancreatic tissue we found a positive reaction only in granulocytes of inflammatory areas with the exception of a luminal reaction on the surface of acinar cells in one case of pancreatic adenocarcinoma. We would like to interpret our results with the hypothesis of granulocytic origin of immunochemically detectable lactoferrin in the pancreatic juice of patients, especially in cases of chronic pancreatitis.

Topics: Adenocarcinoma; Adult; Aged; Breast; Female; Humans; Immunohistochemistry; Lactoferrin; Male; Middle Aged; Milk, Human; Pancreas; Pancreatic Neoplasms; Pancreatitis; Parotid Gland

In 29 patients with chronic pancreatitis, 15 patients with malignant tumours of the pancreas and in 30 controls lactoferrin in fluid aspirated from the duodenum was assessed during the cholecystokinin-secretin (CCK-S) test. As compared with the control group, its concentration is significantly higher in patients with chronic pancreatitis, but not in patients with malignant tumours of the pancreas. It is probable that estimation of lactoferrin in the CCK-S test may prove helpful in the differential diagnosis of pancreatic disease.

Topics: Chronic Disease; Diagnosis, Differential; Duodenum; Humans; Intestinal Secretions; Lactoferrin; Lactoglobulins; Pancreatic Neoplasms; Pancreatitis

Lactoferrin as assayed by a radial immunodiffusion technique was studied in pure pancreatic juice collected at endoscopic retrograde cholangiopancreatography from 23 patients with chronic pancreatitis, 12 with acute pancreatitis, 21 with pancreatic cancer, and 29 cases of nonpancreatic gastrointestinal disease. No clear difference between lactoferrin concentrations in the chronic pancreatitis patients and other groups was found. Moreover, most lactoferrin levels were below the limit of detection in our assay. In addition, lactoferrin total protein ratios did not appear to be of value in the differential diagnosis of chronic pancreatitis. These results seem to be in contrast to the findings of other authors, who measured lactoferrin in duodenal fluid--which is unreliable, in our opinion--or who mainly studied chronic pancreatitis patients and few other pancreatic diseases. Lactoferrin might well be a nonspecific marker for serious pancreatic inflammation.

Topics: Acute Disease; Cholelithiasis; Chronic Disease; Female; Humans; Immunodiffusion; Lactoferrin; Lactoglobulins; Male; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis

Topics: Humans; Lactoferrin; Lactoglobulins; Male; Middle Aged; Pancreatic Neoplasms

Lactoferrin is present in pancreatic juice, and greatly increased concentrations are found in the pancreatic juice of patients with chronic pancreatitis. It is not known whether these high levels of lactoferrin represent a genetically determined defect predisposing to the later development of chronic pancreatitis or are simply a consequence of the disease. In view of the morphological and functional similarities between the pancreatic and parotid glands, we have measured the immunoreactive lactoferrin concentration in pure parotid saliva of 30 patients with chronic calcific pancreatitis, 26 controls, 5 patients with proven pancreatic cancer, 2 patients with Sjögren's disease and 2 patients with chronic recurrent parotitis. No difference in the lactoferrin concentration was detected between control subjects and patients with chronic pancreatitis or pancreatic cancer. Raised levels were found in the 4 patients with parotid gland disease. These findings suggest that increased lactoferrin secretion is confined to the exocrine pancreas in patients with chronic pancreatitis and is thus probably a phenomenon secondary to the disease.

Topics: Calcinosis; Chronic Disease; Humans; Lactoferrin; Lactoglobulins; Pancreatic Neoplasms; Pancreatitis; Parotid Gland; Parotitis; Radioimmunoassay; Saliva; Sjogren's Syndrome; Specimen Handling

Levels of immunoreactive trypsin were measured in pure pancreatic juice obtained endoscopically from 44 patients with suspected pancreatic disease. Patients with pancreatic cancer all had low trypsin concentrations (median 3.6 micrograms/ml, range 0.6--12.0), but those with chronic pancreatitis had very variable levels (median 14.2 micrograms/ml, range 3.2--76.8), showing a considerable overlap with patients without pancreatic disease (median 37.1 micrograms/ml, range 10.4--66.0). When levels of lactoferrin in pancreatic juice were measured, all patients with chronic pancreatitis were found to have much higher levels (all greater than 900 ng/ml) than control subjects or patients with pancreatic cancer (all less than 400 ng/ml). The combined measurement of trypsin and lactoferrin in pure pancreatic juice appeared to be more promising than any other currently available test for the separation of patients with pancreatic cancer from those with chronic pancreatitis.

Topics: Chronic Disease; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Lactoferrin; Lactoglobulins; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay; Trypsin

Lactoferrin, a protein present in pancreatic juice and other exocrine secretions, was measured by radioimmunoassay in pure pancreatic juice obtained by endoscopic cannulation of the pancreatic duct. Lactoferrin concentrations were high in pancreatic juice from patients with chronic pancreatitis, but they were considerably lower in juice from control subjects and patients with carcinoma of the pancreas. The measurement of lactoferrin concentrations in pure pancreatic juice may be useful in the diagnosis of pancreatic diseases.

Topics: Chronic Disease; Diagnosis, Differential; Humans; Lactoferrin; Lactoglobulins; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay

Topics: Diagnosis, Differential; Humans; Lactoferrin; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis