A very rare case of duodenal hemolymphangioma presenting with iron deficiency anemia

AbstractINTRODUCTIONIntraabdominal lymphangiomas account for less than 5% of all lymphangiomas and small intestinal hemolymphangioma is a very rare benign tumor.PRESENTATION OF CASEHere we describe the first case of primary ulcerated duodenal hemolymphangioma in a 24-year-old woman, causing occult bleeding from gastrointestinal tract. She presented with an unexplained refractory iron-deficiency anemia and gastroduodenoscopy revealed an ulcerated and polypoid lesion of the second portion of the duodenum. Partial resection of the duodenum was thus performed and the final pathological diagnosis was hemolymphangioma.DISCUSSIONThere were only two reports, one of a hemolymphangioma of the pancreas invading to the duodenum and another of a small intestinal hemolymphangioma, presenting with gastrointestinal bleeding until May 2012.CONCLUSIONThe aim of this case report is to highlight the difficulty in making an accurate preoperative diagnosis and describe the surgical management of an unusual location for a very rare tumor. To arrive at a definitive diagnosis and exclude malignancy, partial resection of the duodenum was considered to be the required treatment

Personalizing Cancer Pain Therapy: Insights from the Rational Use of Analgesics (RUA) Group

Introduction: A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer. Methods: The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3–4. Results: This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients’ needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction. Conclusion: These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer

A Quartz Crystal Microbalance Immunosensor for Stem Cell Selection and Extraction

A cost-effective immunosensor for the detection and isolation of dental pulp stem cells (DPSCs) based on a quartz crystal microbalance (QCM) has been developed. The recognition mechanism relies on anti-CD34 antibodies, DPSC-specific monoclonal antibodies that are anchored on the surface of the quartz crystals. Due to its high specificity, real time detection, and low cost, the proposed technology has a promising potential in the field of cell biology, for the simultaneous detection and sorting of stem cells from heterogeneous cell samples. The QCM surface was properly tailored through a biotinylated self-assembled monolayer (SAM). The biotin–avidin interaction was used to immobilize the biotinylated anti-CD34 antibody on the gold-coated quartz crystal. After antibody immobilization, a cellular pellet, with a mixed cell population, was analyzed; the results indicated that the developed QCM immunosensor is highly specific, being able to detect and sort only CD34+ cells. Our study suggests that the proposed technology can detect and efficiently sort any kind of cell from samples with high complexity, being simple, selective, and providing for more convenient and time-saving operations

An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor

Urokinase receptor (uPAR) plays a key role in physiological and pathological processes sustained by an altered cell migration. We have developed peptides carrying amino acid substitutions along the Ser88-Arg-Ser-Arg-Tyr92 (SRSRY) uPAR chemotactic sequence. The peptide pyro glutamic acid (pGlu)-Arg-Glu-Arg-Tyr-NH2 (pERERY-NH2) shares the same binding site with SRSRY and competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the G-protein-coupled N-formylpeptide receptor (FPR). pERERY-NH2 is a dose-dependent inhibitor of both SRSRY- and fMLF-directed cell migration, and prevents agonist-induced FPR internalization and fMLF-dependent ERK1/2 phosphorylation. pERERY-NH2 is a new and potent uPAR inhibitor which may suggest the generation of new pharmacological treatments for pathological conditions involving increased cell migration

Plasmatic renin-angiotensin system in normotensive and hypertensive patients hospitalized with COVID-19

Background: Besides its counterbalancing role of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE) 2 is the receptor for the type 2 coronavirus that causes severe acute respiratory syndrome, the etiological agent of COVID-19. COVID-19 is associated with increased plasmatic ACE2 levels, although conflicting results have been reported regarding angiotensin (Ang) II and Ang-(1−7) levels. We investigated plasmatic ACE2 protein levels and enzymatic activity and Ang II and Ang-(1−7) levels in normotensive and hypertensive patients hospitalized with COVID-19 compared to healthy subjects. Methods: Ang II and Ang-(1−7), and ACE2 activity and protein levels were measured in 93 adults (58 % (n = 54) normotensive and 42 % (n = 39) hypertensive) hospitalized with COVID-19. Healthy, normotensive (n = 33) and hypertensive (n = 7) outpatient adults comprised the control group. Results: COVID-19 patients displayed higher ACE2 enzymatic activity and protein levels than healthy subjects. Within the COVID-19 group, ACE2 activity and protein levels were not different between normotensive and hypertensive-treated patients, not even between COVID-19 hypertensive patients under RAS blockade treatment and those treated with other antihypertensive medications. Ang II and Ang-(1−7) levels significantly decreased in COVID-19 patients. When COVID-19 patients under RAS blockade treatment were excluded from the analysis, ACE2 activity and protein levels remained higher and Ang II and Ang-(1−7) levels lower in COVID-19 patients compared to healthy people. Conclusions: Our results support the involvement of RAS in COVID-19, even when patients under RAS blockade treatment were excluded. The increased circulating ACE2 suggest higher ACE2 expression and shedding.Fil: Silva, Mauro Gastón. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Corradi, Gerardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Pérez Duhalde, Juan I.. Hospital San Martín, la Plata; ArgentinaFil: Nuñez, Myriam. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática. Cátedra de Matemáticas; ArgentinaFil: Cela, Eliana Maiten. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Gonzales Maglio, Daniel H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Brizzio, Ana. Hospital San Martín de La Plata; ArgentinaFil: Salazar, Martin Rogelio Enrique. Hospital San Martín de La Plata; ArgentinaFil: Espeche, Walter. Hospital San Martín de La Plata; ArgentinaFil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Glucose metabolism enzymes gene expression analysis and selective metabolic advantage in the progression of colorectal cancer (CRC)

Background: Cancer cells reprogram their metabolism to meet specific bioenergetic/biosynthetic needs. Abnormal expression of energy metabolism enzymes may sustain aggressive phenotypes, therapeutic resistance and it may disclose novel therapeutic targets. We analyzed mRNA expression of glucose metabolism, key-enzyme genes in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of CRC patients (pts) who underwent surgery and systemic therapy for advanced disease. Methods: Tissues of chemotherapy-naive, non-diabetic CRC pts were retrospectively studied by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (HK1) and 2 (HK2), embryonic pyruvate kinase (PKM2), lactate dehydrogenase-A (LDH-A),glucose transporter-1 (SLC2A), voltage-dependent anion-selective channel protein-1 (VDAC1). The RT-qPCR ΔCt values (Cttarget–Ctreference) were used for calculating the expression level of each target gene with B2M and GUSB adopted as reference genes. A preliminary assessment was planned in a random sample of 24/72 enrolled pts (33%) to verify whether differences were detectable. T-test (Tt) and Wilcoxon test (Wt) were used for comparing ΔCt values between tissues (PT versus NM, LM versus NM, PT versus LM). Results: In the 24 pts, assays repeated with B2M and GUSB showed higher PT mRNA expression than NM for HK1 (Tt p = 0.0001; Wt p = 0.0004), LDH-A (Tt p < 0.0001, Wt p < 0.0001), PKM2 (Tt p < 0.0001, Wt p < 0.0001), SCL2A (Tt p < 0.0001, Wt p < 0.0001), VDAC1(Tt p = 0.0002, Wt p = 0.0004). The same significant associations were found when comparing LM versus NM tissues. There was a trend for higher mRNA expression of these genes in LM than in PT, but at this stage differences did not reach statistical significance. Conclusions: These results indicate enhanced glucose uptake (SCL2A, HK), glycolysis (LDH, PKM2) and mithocondrial trafficking (VDAC1) in CRC. Final analysis will include correlations with RAS/RAF mutational status and survival outcomes

Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer

Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (HK-1) and 2 (HK-2), embryonic pyruvate kinase (PKM-2), lactate dehydrogenase-A (LDH-A), glucose transporter-1 (GLUT-1), voltage-dependent anion-selective channel protein-1 (VDAC-1). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied. GLUT-1, LDH-A, HK-1, PKM-2 and VDAC-1 mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for LDH-A expression only. RAS mutation-positive disease was associated with high GLUT-1 mRNA expression levels only. Right-sided colon tumors showed significantly higher GLUT-1, PKM-2 and LDH-A mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic, RAS-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics.The Pharmacogenomics Journal advance online publication, 1 March 2016; doi:10.1038/tpj.2016.13