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One of the hallmarks of cancer cells is increased energy requirements associated with the higher rate of cellular proliferative activity. Metabolic changes in rapidly dividing cancer cells are closely associated with increased uptake of glucose and abnormal activity of lactate dehydrogenase (LDH), which regulates the processing of glucose to lactic acid. As serum LDH levels were found to be commonly increased in cancer patients and correlated with poor clinical outcome and resistance to therapy, the determination of LDH has become a standard supportive tool in diagnosing cancers or monitoring the effects of cancer treatment. The aim of this review is to summarize the current knowledge about methods and the practical utility for measuring both the total LDH and LDH isoenzymatic activities in the diagnosis, prognosis and prediction of cancer diseases.

PurposeTumor progression is associated with cell migration, invasion and metastasis. These processes are accompanied by the activation of specific proteases that are either linked to cellular membranes or are secreted into extracellular spaces. TNF-α is known to play an important role in various aspects of tumor progression. The aim of this work was to assess the effect of TNF-α on the migration of breast cancer cells and, in addition, to assess its association with the location of membrane-associated proteases in lipid rafts.MethodsWound scratch healing and Transwell migration assays were used to study the effect of TNF-α on the migration of both hormone-dependent and hormone-independent breast cancer-derived cells, i.e., MCF7 and MDA-MB-231, respectively. The expression and secretion of three matrix metalloproteases, MMP9, MMP2 and MT1-MMP, and two dipeptidyl peptidases, CD26 and FAP-α, was investigated using RT-PCR, Western blotting and gelatin zymography. In addition, activation of the MAPK/ERK signaling pathway was investigated by Western blotting.ResultsWe found that a TNF-α-induced enhancement of breast cancer cell migration was accompanied by an increased secretion of MMP9, but not MMP2, into the culture media. We also found that TNF-α upregulated the expression of the dipeptidyl peptidases CD26 and FAP-α in a dose-dependent manner and, in addition, enhanced the concentration of all five proteases in lipid rafts in the breast cancer-derived cells tested, regardless of cell type. Furthermore, we found that TNF-α activated the MAPK/ERK signaling pathway by increasing the ERK1/2 phosphorylation level. Application of the MEK/ERK1/2 inhibitor U-0126 resulted in down-regulation of TNF-α-induced MMP9 secretion and abrogation of the enhanced concentration of proteases in the lipid rafts.ConclusionsFrom our results we conclude that TNF-α-induced activation of the MAPK/ERK signaling pathway may promote breast cancer cell migration via both upregulation of MMP9, CD26 and FAP-α and concentration of these proteases, as also MT1-MMP and MMP2, in the lipid rafts. TNF-α may serve as a potential therapeutic target in breast cancers susceptible to TNF-α stimulation.

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Colonic diverticular disease is the most common cause of lower gastrointestinal bleeding. In the past, this condition was usually managed with urgent colectomy. Recently, the development of endoscopy and interventional radiology has led to a change in the management of colonic diverticular bleeding.The aim of this systematic review is to define the best treatment for colonic diverticular bleeding.A systematic bibliographic research was performed on the online databases for studies (randomized controlled trials [RCTs], observational trials, case series, and case reports) published between 2005 and 2014, concerning patients admitted with a diagnosis of diverticular bleeding according to the PRISMA methodology.The outcomes of interest were: diagnosis of diverticulosis as source of bleeding; incidence of self-limiting diverticular bleeding; management of non self-limiting bleeding (endoscopy, angiography, surgery); and recurrent diverticular bleeding.Fourteen studies were retrieved for analysis. No RCTs were found. Eleven non-randomized clinical controlled trials (NRCCTs) were included in this systematic review. In all studies, the definitive diagnosis of diverticular bleeding was always made by urgent colonoscopy. The colonic diverticular bleeding stopped spontaneously in over 80% of the patients, but a re-bleeding was not rare. Recently, interventional endoscopy and angiography became the first-line approach, thus relegating emergency colectomy to patients presenting with hemodynamic instability or as a second-line treatment after failure or complications of hemostasis with less invasive treatments.Colonoscopy is effective to diagnose diverticular bleeding. Nowadays, interventional endoscopy and angiographic treatment have gained a leading role and colectomy should only be entertained in case of failure of the former.

Background: Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumours in the digestive tract. The duodenal GIST (dGIST) is the rarest subtype, representing only 4-5% of all GIST, but up to 21% of the resected ones. The diagnostic and therapeutic management of dGIST may be difficult due to the rarity of this tumor, its anatomical location, and the clinical behavior that often mimic a variety of conditions; moreover, there is lack of consent for their treatment. This study has evaluated the scientific literature to provide consensus on the diagnosis of dGIST and to outline possible options for surgical treatment.Methods: An extensive research has been carried out on the electronic databases MEDLINE, Scopus, EMBASE and Cochrane to identify all clinical trials that report an event or case series of dGIST.Results: Eighty-six studies that met the inclusion criteria were identified with five hundred forty-nine patients with dGIST: twenty-seven patients were treated with pancreatoduodenectomy and ninety-six with only local resection (segmental/wedge resections); in four hundred twenty-six patients it is not possible identify the type of treatment performed (pancreatoduodenectomy or segmental/wedge resections).Conclusions: dGISTs are a very rare subset of GISTs. They may be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumours smaller than 2 cm have a low biological aggressiveness and can be followed annually by endoscopic ultrasound. The biggest ones should undergo radical surgical resection (R0). In dGIST there is no uniformly adopted surgical strategy because of the low incidence, lack of experience, and the complex anatomy of the duodenum. Therefore, individually tailored surgical approach is recommended. R0 resection with 1-2 cm clear margin is required. Lymph node dissection is not recommended due to the low incidence of lymphatic metastases. Tumor rupture should be avoided.

Having the capability to proteolyze diverse structural and signaling proteins, matrix metalloproteinase 9 (MMP9), one of the best-studied secretory endopeptidases, has been identified as a crucial mediator of processes closely associated with tumorigenesis, such as the extracellular matrix reorganization, epithelial to mesenchymal transition, cell migration, new blood vessel formation, and immune response. In this review, we present the current state of knowledge on MMP9 and its role in cancer growth in the context of cell adhesion/migration, cancer-related inflammation, and tumor microenvironment formation. We also summarize recent achievements in the development of selective MMP9 inhibitors and the limitations of using them as anticancer drugs.

Rationale:Retroperitoneal colonic perforation is a rare cause of retroperitoneal abscess. It presents, more frequently in frail elderly patients, with heterogeneous signs and symptoms which hamper the clinical diagnosis. Subcutaneous emphysema with pneumomediastinum and iliopsoas muscle abscess are unusual signs. Colonic retroperitoneal perforation may be consequent to diverticulitis or locally advanced colon cancer. Due to the anatomy of the retroperitoneal space and different physiopathology, diverticular perforation may present with air and pus collection; on the other hand perforated colon cancer may cause groin mass and psoas abscess. We reported 2 cases of colonic retroperitoneal perforation from diverticulitis and locally advanced colon cancer, respectively. Aim of this report is to improve differential diagnosis based on clinical signs.Patients’ concerns:A 71-year-old man presented with pain in his left side, fatigue, fever, nausea, massive subcutaneous emphysema of the neck, and Blumberg sign in the left iliac fossa. A 67-year-old man presented with abdominal pain, sub-occlusion, left groin mass, left groin, and lower limb pain during walking, negative Blumberg sign.Diagnosis:In the first patient the computerized tomography revealed pneumoperitoneum, gas in the mesosigma, pneumomediastinum, wall thickening of the descending colon, and retroperitoneal collection from diverticular perforation. In the second patient abdominal CT scan found thickening of the sigmoid colon adherent to the iliopsoas and fluid collection.Interventions:In the first patient, a left hemicolectomy extending to the transverse colon, followed by a toilette and debridement of the retroperitoneum were performed. In the second patient, tumor of descending colon perforated in the retroperitoneum with iliopsoas abscess was treated with left hemicolectomy and a drainage of the abscess.Outcomes:The first patient underwent right colectomy with ileostomy in the 7th postoperative day for large bowel necrosis. He died of sepsis 2 days after. The second patient had regular postoperative and he is still alive.Lessons:The spread of retroperitoneal abscess in complicated colonic diverticulitis is different from that in advanced colonic cancer. The former can present with a subcutaneous emphysema, the latter with a groin mass. Hence a thorough clinical examination and radiological studies are needed to diagnose these conditions.