The mechanism of sitagliptin inhibition of colorectal cancer cell lines' metastatic functionalities.

The cell membrane glycoprotein CD26 with peptidase activity (DPP4) and/or its soluble CD26/DPP4 counterpart expression and/or activity are altered in several cancers. Its role in metastasis development was recently highlighted by the discovery of CD26+ cancer stem cell subsets and the fact that clinical DPP4 inhibitors showed antimetastatic effects in animal models. Also, diabetic patients treated with the DPP4 inhibitor sitagliptin showed greater overall survival after colorectal or lung cancer surgery than patients under other diabetic therapies. However, the mechanism of action of these inhibitors in this context is unclear. We studied the role of CD26 and its DPP4 enzymatic activity in malignant cell features such as cell-to-cell homotypic aggregation, cancer cell motility, and invasion in a panel of human colorectal cancer (CRC) cell lines, avoiding models that include the physiological role of DPP4 in chemotaxis. Present results indicate that CD26 participates in the induction of cell invasion, motility, and aggregation of CD26-positive CRC cell lines. Moreover, only invasion and motility assays, which are collagen matrix-dependent, showed a decrease upon treatment with the DPP4 inhibitor sitagliptin. Sitagliptin showed opposite effects to those of transforming growth factor-ß1 on epithelial-to-mesenchymal transition and cell cycle, but this result does not explain its CD26/DPP4-dependent effect. These results contribute to the elucidation of the molecular mechanisms behind sitagliptin inhibition of metastatic traits. At the same time, this role of sitagliptin may help to define areas of medicine where DPP4 inhibitors might be introduced. However, they also suggest that additional tools against CD26 as a target might be used or developed for metastasis prevention in addition to gliptins.

Complementary and Integrative Medicine Use in Individuals Seeking Conventional Medical Oncology Care in Chile: Prevalence and Patient Characteristics.

PURPOSE: Complementary and integrative medicine (CIM) use during cancer care has increased in Western medical settings. Little is known about interest in and use of CIM approaches by oncology patients in Chile and South America. PATIENTS AND METHODS: Patients presenting for conventional outpatient or inpatient medical oncology care at the Clinica Alemana in Santiago, Chile, from March to June 2017 were asked to complete a survey about their interest in and use of CIM approaches. Goals included determining the prevalence of CIM use and exploring associations between CIM use and patient characteristics. Statistical analyses included a two-tailed t test for continuous variables, Fischer's exact test for categorical variables, and logistic regression for association between CIM use and other variables. RESULTS: Of 432 patients surveyed, 66.9% were diagnosed with breast cancer, 84.8% were women, the majority of patients (58.1%) were between age 40 and 60 years, and 51.5% (n = 221) reported CIM use. No association was found between CIM use and the sociodemographic variables of sex, age, education, or income. In all, 44.6% of patients with breast cancer reported CIM use compared with 64.8% of patients with other cancer types (P > .001). Most commonly reported types of CIM used included herbals (49.1%), vitamins and minerals (40.8%), and prayer or meditation (40.4%). Most frequent reasons for CIM use were to "do everything possible" (72%) and to "improve my immune function" (67.8%). Most patients (43.4%) reported starting CIM use at the time of cancer diagnosis, with only 55.4% sharing information regarding CIM use with their medical team. CONCLUSION: The majority of patients surveyed reported engaging in CIM use, with just over half the users communicating with their oncology team about their CIM use. Increased awareness of regional differences in CIM use may help increase communication regarding this subject and contribute to improved outcomes.

Surface expression marker profile in colon cancer cell lines and sphere-derived cells suggests complexity in CD26+ cancer stem cells subsets.

Taking advantage of eight established cell lines from colorectal cancer patients at different stages of the disease and the fact that all of them could form spheres, cell surface biomarkers of cancer stem cells and epithelial-mesenchymal transition were tested. The aim was to investigate cancer stem cells and metastatic stem cells in order to provide functional characterization of circulating tumor cells and promote the development of new anti-metastatic therapies. Our model showed an important heterogeneity in EpCAM, CD133, CD44, LGR5, CD26 and E-cadherin expression. We showed the presence of a subset of E-cadherin+ (some cells being E-cadherinhigh) expressing CD26+ (or CD26high) together with the well-known CSC markers LGR5 and EpCAMhigh, sometimes in the absence of CD44 or CD133. The already described CD26+/E-cadherinlow or negative and CD26+/EpCAM-/CD133- subsets were also present. Cell division drastically affected the expression of all markers, in particular E-cadherin, so new-born cells resembled mesenchymal cells in surface staining. CD26 and/or dipeptidyl peptidase 4 inhibitors have already shown anti-metastatic effects in pre-clinical models, and the existence of these CD26+ subsets may help further research against cancer metastasis.

[Liver transplantation in adults: a caseload from Clínica Alemana de Santiago, Chile]. / Trasplante hepático en adultos: casuística de Clínica Alemana de Santiago.

BACKGROUND: The success of orthotopic liver transplantation (OLT) has resulted in its widespread use for different liver diseases. AIM: To report our 8 years experience with adult OLT at Clinica Alemana de Santiago. PATIENTS AND METHODS: In all transplantations done at the center, we recorded patient's overall data and survival, postoperative medical and surgical complications and causes of death. RESULTS: Between November 1993 and September 2001, 51 consecutive OLT were performed in 44 patients (22 females, median age 45 years old). Thirty eight patients presented with chronic and 6 with acute or sub-acute liver failure. Cryptogenic cirrhosis and hepatitis C infection were the most common causes for OLT. Postoperative bleeding and extrahepatic biliary complications were seen in 17.6 and 21.5% of cases respectively. Acute rejection, bacterial infections, CMV infection or disease and post OLT hemodialysis were the most common medical complications (51, 31, 19.6 and 19.6% of cases respectively). The overall 1 and 5 years survival rates were 80% and 73% respectively. Considering exclusively the last 22 OLT performed since January 1999, the 1 year survival rate has improved to 91%. CONCLUSIONS: Liver transplantation in Chile provides a good long term survival with acceptable morbidity, due to a multidisciplinary approach management. The survival rates have improved over the last few years probably due to better surgical techniques, ICU care and immunosuppression. These overall results are comparable with those from other Centers in developed countries.

Evaluación del dolor postoperatorio en cirugía de hemiabdomen superior bajo cinco esquemas de analgesia / Evaluation of postoperatory pain in upper hemiabdominal surgery under 5 schemes of analgesia

Sesenta y nueve pacientes ASA I y II sometidos a cirugía de hemiabdomen superior, fueron asignados al azar a uno de 5 esquemas analgésicos, iniciados en la inducción anestésica y mantenidos durante 24 horas: I: ketoprofeno 100 mg IV c/8 horas. II: fentanyl 4 µg/kg en bolo + infusión de 1 µg/kg-1/h-1. III: morfina 4 mg vía peridural lumbar. IV: metadona 0,1 mg/kg IM c/8 h. V: morfina 0,1 mg/kg en bolo + infusión de 10 µg/kg-1/h-1. Fueron evaluados por un observador entrenado que desconocía el esquema utilizado, a través de: 1) Escala visual análoga (EVA); 2) Escala de valoración verbal (EVV) en reposo; 3) Fascie del paciente en reposo y en movimiento; 4) EVV retrospectiva; 5) Número de analgésicos adicionales; 6) Aceptabilidad al método. Las evaluaciones se hicieron a las 2, 4, 6, 12, 24, 36, 48 horas de iniciado el esquema, consignándose además: FR, PA, FC, presencia de náuseas, vómitos, retención urinaria, prurito y grado de sedación. Se controló gases en sangre arterial a las 2, 12 y 24 horas. Se hizo ANOVA + t-Test o Chi cuadrado, según correspondía. Todos los grupos fueron comparables. Hubo mejor analgesia en los grupos II, III y IV, habiendo diferencia significativa para el grupo II. Todos lod grupos requirieron analgésicos adicionales, siendo el promedio menor en el grupo II. No hubo diferencia intergrupo en cuanto a náuseas, vómitos y retención urinaria. La aceptabilidad al método fue buena. La PaO2 fue similar en todos los grupos. No hubo retención de CO2 en ningún grupo, siendo la PaCO2 significativamente menor en el grupo I. Hubo alivio del dolor con los 5 esquemas utilizados, siendo mejor el esquema II. Tuvimos buena aceptación al método y no hubo complicaciones inherentes a él