The role of macrophages and mast cells in lymphangiogenesis and angiogenesis in cervical carcinogenesis.

During carcinogenesis it is known that growth factors and cytokines from stromal and inflammatory cells from the microenvironment promote angiogenesis and lymphangiogenesis. However, the participation of macrophages and mast cells in these processes is not well understood. The aim of this study was to evaluate the relationship between mast cell and macrophage density with blood and lymphatic vessels in various stages of carcinoma of the uterine cervix. Tissue sections from archival paraffin-embedded samples from cases with cervical intraepithelial neoplasias (CIN) 1, 2, 3, carcinoma in situ, and invasive carcinoma were used. Immunohistochemical staining was done using the following antibodies: anti-LYVE-1; anti-CD31; anti-CD68, and anti-tryptase. Our results showed a significant increase in the number of macrophages in carcinoma in situ, a correlation between lymphatic vessels and macrophages in premalignant lesions CIN 2, and a correlation between mast cells and blood vessels in both CIN 2 and carcinoma in situ. In conclusion, our data underscore the importance of the recruitment of macrophages and mast cells in the development of tumor-associated blood and lymphatic capillaries.

[Cancer lymphangiogenesis and its role in metastasic dissemination]. / Linfangiogénesis en el cáncer y su papel en la diseminación metastásica.

It is well-known that there are different tumor-type-dependent metastatic patterns. For example, in carcinomas metastatic spread is preferentially via the lymphatic system by which they reach regional lymph nodes through pre-existent afferent lymph vessels and/or newly formed lymph capillaries; while in sarcomas the favored pathway is through bloodvessels. These metastatic patterns have been used for many years by clinicians and surgeons for staging and tumor resection, particularly in the case of breast cancer. Recently this knowledge has been applied to detection and resection of sentinel lymph nodes. The lymphatic system drains the interstitial fluid from tissues and reincorporates it into the blood flow; in addition, it forms part of the host's immune defense and in pathological conditions, induces different types of lymph edema and participates in tumor invasion and metastasis. Although, the study of lymphangiogenesis was stagnated for several decades, it was not until a few years ago that biomolecular mechanisms were discovered and many specific markers are now in use to study the process of tumor dissemination and metastasis. There is a tendency to utilize molecular knowledge in clinical settings for grading and estimating prognostic significance of tumors as well as to develop specific therapeutic strategies.

Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes.

Apoptosis of granulosa cells during follicular atresia is preceded by oxidative stress, partly due to a drop in the antioxidant glutathione (GSH). Under oxidative stress, GSH regeneration is dependent on the adequate supply of NADPH by glucose-6-phosphate dehydrogenase (G6PD). In this study, we analyzed the changes of G6PD, GSH, and oxidative stress of granulosa cells and follicular liquid and its association with apoptosis during atresia of small (4-6 mm) and large (>6 mm) sheep antral follicles. G6PD activity was found to be higher in granulosa cells of healthy small rather than large follicles, with similar GSH concentration in both cases. During atresia, increased apoptosis and protein oxidation, as well as a drop in GSH levels, were observed in follicles of both sizes. Furthermore, the activity of G6PD decreased in atretic small follicles, but not in large ones. GSH decreased and protein oxidation increased in follicular fluid. This was dependent on the degree of atresia, whereas the changes in G6PD activity were based on the type of follicle. The higher G6PD activity in the small follicles could be related to granulosa cell proliferation, follicular growth, and a lower sensitivity to oxidative stress when compared with large follicles. The results also indicate that GSH concentration in atretic follicles depends on other factors in addition to G6PD, such as de novo synthesis or activity of other NADPH-producing enzymes. Finally, lower G6PD activity in large follicles indicating a higher susceptibility to oxidative stress associated to apoptosis progression in follicle atresia.

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos.

AIM: The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus. METHODS: A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method. RESULTS: Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P

Linfangiogénesis en el cáncer y su papel en la diseminación metastásica / Cancer lymphangiogenesis and its role in metastasic dissemination

Es bien sabido que existen diferentes patrones de metástasis dependiendo del tipo tumoral. Por ejemplo, la diseminación metastásica de los carcinomas es vía linfática preferencialmente, las células neoplásicas llegan a los ganglios linfáticos regionales a través de vasos linfáticos aferentes preexistentes o capilares linfáticos de nueva formación; en cambio, en los sarcomas la vía principal es a través de los vasos sanguíneos. Estos patrones metastásicos han sido utilizados durante muchos años por los clínicos y cirujanos para la etapificación y resección tumoral, particularmente en cáncer de mama. Recientemente este conocimiento ha sido aplicado para la detección y resección del ganglio centinela. El sistema linfático drena el líquido intersticial de los tejidos y lo reincorpora al sistema sanguíneo; además, forma parte de la defensa inmune del huésped y en condiciones patológicas induce diferentes tipos de linfedema y participa en la invasión y metástasis. El estudio de la linfangiogénesis permaneció aletargado por muchas décadas y no es sino hasta los últimos años que se han descrito mecanismos biomoleculares y marcadores específicos, los cuales actualmente se están utilizando para estudiar el proceso de diseminación tumoral y metástasis. Existe una tendencia hacia la aplicación clínica de este conocimiento molecular en la clínica para estimar el significado pronóstico de los tumores, así como para desarrollar estrategias terapéuticas específicas.

It is well-known that there are different tumor-type-dependent metastatic patterns. For example, in carcinomas metastatic spread is preferentially via the lymphatic system by which they reach regional lymph nodes through pre-existent afferent lymph vessels and/or newly formed lymph capillaries; while in sarcomas the favored pathway is through bloodvessels. These metastatic patterns have been used for many years by clinicians and surgeons for staging and tumor resection, particularly in the case of breast cancer. Recently this knowledge has been applied to detection and resection of sentinel lymph nodes. The lymphatic system drains the interstitial fluid from tissues and reincorporates it into the blood flow; in addition, it forms part of the host's immune defense and in pathological conditions, induces different types of lymph edema and participates in tumor invasion and metastasis. Although, the study of lymphangiogenesis was stagnated for several decades, it was not until a few years ago that biomolecular mechanisms were discovered and many specific markers are now in use to study the process of tumor dissemination and metastasis. There is a tendency to utilize molecular knowledge in clinical settings for grading and estimating prognostic significance of tumors as well as to develop specific therapeutic strategies.

Crosstalk between coagulation and inflammation during Dengue virus infection.

Dengue fever is the most prevalent viral disease transmitted by vectors (Aedes aegypti, Aedes albopictus) in worldwide. More than 100 million cases occur annually with a mortality rate of 5% and no safe vaccine is available. The pathogenesis of Dengue, where host and viral factors participate in the establishment of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS) remains unresolved. Clinical observations have revealed significant abnormalities in coagulation and inflammation systems, with increased levels of tissue factor (TF) and the chemokine IL-8, correlating with the severity of the disease and implicating damage to endothelial vascular cells (EVC). Here we present novel insights concerning the crosstalk between the regulatory signaling pathways of the coagulation-inflammation processes, during Dengue virus (DV) infection of EVC. We found that DV up-regulates Protease Activated receptor type-1 (inflammation) and TF (coagulation) receptors, via the phosphorylation of p38 and ERK1/2 MAPKs, which favor the activation of NF-kappaB transcription factor. This induces pro-inflammatory (IL-8) or pro-adhesive (VCAM-1) gene expression which may lead to EVC activation. The elucidation of the basic principles that signal these processes has important implications for the design of new therapeutic strategies for DHF/DSS.