Coevolución genética Homo sapiens-Helicobacter pylori y sus implicaciones en el desarrollo del cáncer gástrico: una revisión sistemática / A Systematic Review of Genetic Coevolution of Homo Sapiens and Helicobacter Pylori: Implications for Development of Gastric Cancer

Helicobacter pylori (H. pylori), clasificada como carcinógeno tipo I para cáncer gástrico (CG), ha acompañado al hombre al menos desde hace 116 000 años. Los conocimientos de las fuerzas evolutivas que modulan el rol de esta bacteria en el desarrollo del espectro de enfermedades gástricas son aún escasos. Esta revisión sistemática recopila artículos que reportan un proceso de coevolución, relacionan los componentes ancestrales huésped-hospedero y describen mecanismos adaptativos de H. pylori al entorno gástrico humano, con el fin de comprender si el proceso de coevolución modula la patogenicidad de la bacteria y el desarrollo de enfermedades gástricas. Se realizó una búsqueda sistemática en las bases de datos electrónicas: MEDLINE (OvidSP), Scopus (ScienceDirect), Scielo y Tree of Science (ToS); términos de búsqueda: "stomach", "cancer", "neoplasms", "ethinicity", "evolution", "genetics", "ancestry" y "Helicobacter pylori". Idiomas: inglés y español. Los datos fueron filtrados por un revisor utilizando un formulario estándar de extracción y ulteriormente revisados por otro. El riesgo de sesgo y la calidad metodológica de los estudios fueron evaluadas con el programa: Critical Appraisal Skills Programme (CASP). Del total de 1584 estudios, 36 cumplieron los criterios de inclusión. Los factores más relevantes en el desarrollo del espectro de enfermedades asociadas con la infección por H. pylori son: la disrupción en el proceso de coevolución entre la bacteria y su huésped humano -por la transferencia horizontal de segmentos de genes que no han evolucionado con sus anfitriones-; las sustituciones de aminoácidos; la fijación y la selección positiva principalmente en las regiones hipervariables.

Helicobacter pylori (H. pylori) is classified as carcinogen type I for gastric cancer (GC). Although it has accompanied man for at least 116,000 years, knowledge of the evolutionary forces that modulate the role of this bacterium within the development of the spectrum of gastric diseases is still scarce. This systematic review compiles articles that report a process of coevolution process, relate host-host ancestral components, and describe H. pylori’s mechanisms of adaptation to the human gastric environment in order to understand if coevolution has modulated the pathogenicity of these bacteria and the development of gastric diseases. A systematic search was carried out in MEDLINE (OvidSP), Scopus (ScienceDirect), Scielo and Tree of Science (ToS). The following search terms were used: "Stomach", "Cancer", "Neoplasms", "Ethinicity", "Evolution", "Genetics", "Ancestry" and "Helicobacter pylori", and searches were conducted in both English and Spanish. The data were filtered by one reviewer using a standard extraction form and then reviewed by another. The risk of bias and the methodological quality of the studies were evaluated using the Critical Appraisal Skills Program (CASP). Thirty-six of the total 1,584 studies found met the inclusion criteria. The most relevant factors in the development of the spectrum of diseases associated with H. pylori infection are amino acid substitutions, binding and positive selection mainly in the hypervariable regions, and disruption of the coevolution process between the bacteria and their human hosts as the result of horizontal transfer of gene segments that did not evolve with their host.

Intrinsic caspase-8 activation mediates sensitization of erlotinib-resistant tumor cells to erlotinib/cell-cycle inhibitors combination treatment.

Inhibitors of the tyrosine kinase activity of epidermal growth factor receptor, as erlotinib, have an established role in treating several cancer types. However, resistance to erlotinib, particularly in breast cancer cell lines, and erlotinib treatment-associated disorders have also been described. Also, methods and combination therapies that could reverse resistance and ameliorate non-desirable effects represent a clinical challenge. Here, we show that the ATP non-competitive CDK2/cyclin A inhibitor NBI1 sensitizes erlotinib-resistant tumor cells to the combination treatment (co-treatment) for apoptosis-mediated cell death. Furthermore, in erlotinib-sensitive cells, the effective dose of erlotinib was lower in the presence of NBI1. The analysis in the breast cancer MDA-MB-468 erlotinib-resistant and in lung cancer A549 cell lines of the molecular mechanism underlying the apoptosis induced by co-treatment highlighted that the accumulation of DNA defects and depletion of cIAP and XIAP activates the ripoptosome that ultimately activates caspases-8 and -10 and apoptosis. This finding could have significant implications for future treatment strategies in clinical settings.

Is the ancillary chemotherapy approach of any value in the treatment of infratentorial primitive neuroectodermal tumors with surgery and radiotherapy?

A retrospective historical analysis of patients under 18 years of age with the histopathological diagnosis of infratentorial primitive neuroectodermal tumor (PNET) is presented. The survey embraced two different groups of children. Group 1 was defined as those patients treated from 1972 to 1984 with surgical resection plus neuraxis radiotherapy alone. Group 2 was made up of children treated from 1990 to 1996 with the same approach but with the addition of adjuvant chemotherapy: cisplatin (day 1) and etoposide (days 1-3) every 3 weeks for 6 months. Group 1 embraced 42 children with an age range of 1-16 years (mean 6 years, SD 4.4 years). In group 2 there were 34 children, their ages ranging from 1 to 18 years (mean 7.2, SD 4.6 years). The prevalence of stages T2M0 and T3M0 was similar in both groups, but in group 1 there were 4 patients (9.5%) whose spinal fluid was positive for tumor cells (M1), while in group 2 there were 7 children (20.5%) with positive spinal fluid. There was an unequivocal initial response to treatment in 86% of these children in group 1 and in 79% in group 2. The event-free survival (EFS) was 30% at 252 months in group 1, while for group 2 the EFS was 67.6% at 63 months (P 0.002). Mortality from tumor activity was noted in 26 patients (70%) in group 1, while in group 2 mortality attributable to tumor progression was documented in 11 children (32%). We conclude that the use of adjuvant chemotherapy in these patients improves survival without any significant morbidity.

[Lymphoblastic lymphoma in children. Poor response in advanced disease with chemotherapy for non-Hodgkin's lymphoma]. / Linfoma linfoblástico en niños. Respuesta pobre en enfermedad avanzada con quimioterapia de linfoma no Hodgkin.

Fifty three pediatric patients with the histopathological diagnosis of lymphoblastic lymphoma (LL) were studied in a retrospective analysis during a 14 year period. Their age ranged from 1 to 16 years with a median of 7 years. Clinical staging was performed according to Murphy's system. There was one child in stage I (2%), 11 in stage II (21%), 14 stage III (26%) and 27 stage IV (51%). Patients in stage IV, 21 (78%) had initial bone marrow involvement, 4 (15%) central nervous system (CNS) infiltration and 2 (7%) simultaneous infiltration to the bone marrow and the CNS. The chemotherapy program consisted of induction, consolidation and maintenance with CNS prophylaxis. The whole program lasted 36 months. Out of 53 patients there were only 45 evaluable for treatment analysis response. A total of 14 (31%) are alive and in a continuous complete remission, with a median duration of remission of 66 months, 8 (18%) children abandoned treatment with a median duration of remission of 10 months. Twenty three patients (51%) are dead. The actuarial survival at 11 year is of 39% +/- 11% with a median remission rate for the whole group of 11.8 months. No patient in complete remission for more than 24 months has relapsed. We conclude that our chemotherapy program is more than adequate for early stages, but for advanced disease it has been a failure. There is a need to modify the chemotherapy program using a very similar protocol as the one used in high risk childhood acute lymphoblastic leukemia.

[Giardia lamblia extract (giardine): its immunologic mechanism]. / Extracto de Giardia lamblia (giardina): su mecanismo inmunológico.

Giardia lamblia is a protozoa that invades the high portions of human small bowel, as well the gall bladder and biliary passages. The absorption from the gut of extrinsic particles which have all properties occurs at full scale in the small bowel. Infections by this protozoa may lead to different clinical symptoms: departing free-symptom, urticarial manifestations of variable intensity and malabsorption syndromes, as well. In Cuba, Giardia lamblia parasitism constitutes a health problem because of its high incidence and prevalence. Investigators have showed allergic dermatological disorders and others, in patients with giardiasis, that may obey from two mechanisms: first, the parasite or its metabolic products might be antigenic for the host; second, the parasite may act as a hapten, that in successive sensitizations might lead to such manifestations, producing specific antibodies which have been found in patients' sera with giardiasis. We recently have elaborated an allergenic extract from Giardia lamblia (we called it giardine ), for demonstrating cutaneous sensitization to such protozoa. In other way, Prausnitz and Küstner, in 1921, showed that a dermal allergic reaction could be passively transferred by means of sensitized patient's serum to a non-sensitized subject. More recently, in 1967, Ishizaka and Ishizaka and Johansson and Benich, in separate studies, showed that skin sensitizing antibodies belonged to a different kind of immunoglobulin, IgE, and it could be measured in serum from sensitized patients. So, a study of sensitization to Giardia lamblia has been performed. Twenty-two patients have been studied suffering from giardiasis with at least 3 month evolution of this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitroglycerin inhibits experimental thrombosis and reocclusion after thrombolysis.

Nitroglycerin inhibits platelet aggregation in vitro, but its effect on thrombosis and platelet function in vivo is controversial. This study assessed the effect of nitroglycerin on primary thrombus formation in response to vessel wall injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protocol the right carotid artery was instrumented with a flow probe, stenosis, an anodal electrode, and a proximal infusion line. A 300 microA anodal current was used to induce endothelial injury and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin (1 microgram/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dogs (p < 0.05). In the second protocol both carotid arteries were instrumented as described previously. Anodal current (300 microA, 180 minutes) was applied to the right carotid (n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel, receiving either nitroglycerin (1 microgram/kg/min intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs control value) and inhibited ex vivo platelet aggregation to adenosine diphosphate and arachidonic acid (p < 0.05). Local infusion of nitroglycerin reduced the formation of primary thrombi, independent of the hypotensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduced the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitroglycerin therapy may be derived from its ability to inhibit thrombotic events in patients with unstable angina or myocardial infarction.

[Wilms' tumor. Its multidisciplinary management]. / Tumor de Wilms. Manejo multidisciplinario.

A total of 115 children with a histopathological diagnosis of Wilms' tumor were studied. The average age was three years. An abdominal tumor was the most frequent clinical manifestations, with a predominating clinicopathological stage II. The most important prognostic factors were the clinical stage and histological subvariety. A five year disease free period during the early stages was very favorable. On the other hand, advances stages and unfavorable histopathology established a poor prognosis. In our experience, stages I and II and favorable histology should not receive radiotherapy but instead brief chemotherapy. The global five year survival was 82%. All the patients with an unfavorable histology occupied stages II and IV. a comparison of disease free survival between stages I and II against III and IV showed statistical significance (p 0.01). Statistical significance also appeared upon comparison between unfavorable versus favorable (p 0.01) histology. Emphasis is placed upon multidisciplinary management of this type of malignant neoplasias.

Treatment of non-Hodgkin's lymphoma in Mexican children. The effectiveness of chemotherapy during malnutrition.

The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6%). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2%). The most common histology was diffuse undifferentiated non-Burkitt type (37.4%). According to the Murphy staging system, 40.1% were stage III and 27.2% were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine, and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7%. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69% at 2 years and 63% at 6 years, compared with 36% at 6 years of the control group (COP) (p less than 0.01). None of the patients have relapsed after 4 years.