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Studying the complex mechanisms of tumorigenesis and examining the interactions of neoplastic cells within tumor ecosystem are critical to explore the possibility of effective cancer treatment modalities. Dynamic tumor ecosystem is constantly evolving and is composed of tumor cells, extracellular matrix (ECM), secreted factors, and stromal cancer-associated fibroblasts (CAF), pericytes, endothelial cells (EC), adipocytes, and immune cells. ECM remodeling by synthesis, contraction, and/or proteolytic degradation of ECM components and release of matrix-sequestered growth factors create a microenvironment that promotes EC proliferation, migration, and angiogenesis. Stromal CAFs release multiple angiogenic cues (angiogenic growth factors, cytokines, and proteolytic enzymes) which interact with ECM proteins, thus contribute to enhance proangiogenic/promigratory properties and support aggressive tumor growth. Targeting angiogenesis brings about vascular changes including reduced adherence junction proteins, basement membrane and pericyte coverage, and increased leakiness. This facilitates ECM remodeling, metastatic colonization and chemoresistance. Owing to significant role of denser and stiffer ECM in inducing chemoresistance, direct or indirect targeting of ECM components is being reported as major axis of anticancer treatment. Exploring the agents targeting angiogenesis and ECM in a context specific manner may lead to reduced tumor burden by promoting conventional therapeutic effectiveness and overcoming the hurdles of therapy resistance.
Asunto(s)
Ecosistema , Neoplasias , Humanos , Células Endoteliales , Matriz Extracelular , Carcinogénesis , Microambiente TumoralRESUMEN
BACKGROUND: The aim of this study is to clinically evaluate and compare the clinical success and the relative bone healing of the implants which are placed using a flapless procedure and compare it to those placed by the conventional flap technique. MATERIALS AND METHODS: This study was conducted with ten patients that were randomly divided into two groups. Group A included patients with immediately placed implants after extraction with flap elevation. Group B included patients with immediately placed implants after extraction without any flap elevation. The clinical parameters recorded were Plaque index, Modified Gingival Index, Early Wound Healing Index, Buser's criteria, Distance between implant shoulder and the crestal bone (DIB), and Radiographic Examination in a standardized manner to evaluate changes for the DIB values. RESULTS: There was an improvement in Plaque Score from baseline to 1 month and baseline to abutment placement (6 months), which was statistically significant, but the plaque score from 3 months to abutment placement (6 months) was statistically nonsignificant in both the group. There was an increase in modified gingival score from baseline to 3 months, baseline to abutment placement (6 months), and 3 months to abutment placement (6 months), which was statistically significant in both the groups. The DIB scores in Group A recorded at baseline to 6 months were 2.80 ± 0.57 and 1.90 ± 0.42, respectively, showing a mean difference of -0.90 and P = 0.001 in comparison. Whereas, the DIB scores in Group B at baseline to 6 months were 3.20 ± 0.57 and 2.50 ± 0.50, respectively, showing a mean difference of -0.70 and P = 0.001 in comparison. The DIC scores in Group A at baseline to 6 months were 1.60 ± 0.54 and 0.00 ± 0.00, respectively, showing a mean difference of -1.60 and P = 0.003 in comparison, Whereas the DIC scores in Group B at baseline to 6 months were 1.40 ± 0.54 and 0.00 ± 0.00, respectively, showing a mean difference of -1.40 and P = 0.005 in comparison. CONCLUSION: Implants placed in fresh extraction sockets with and without mucoperiosteal flap elevation can be successfully done with augmentation procedures. Short-term survival rates and clinical outcomes of both groups were similar and appeared to be predictable treatment modalities.
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BACKGROUND: The aim is to assess the effect of periodontal therapy and scaling and root planing (SRP) on the metabolic control in Type 2 diabetes mellitus (DM) patients with chronic periodontitis based on the estimation of glycated hemoglobin (HbA1c). MATERIALS AND METHODS: A prospective, comparative, clinical study was performed on 50 patients suffering from Type 2 DM with moderate, generalized chronic periodontitis. Type 2 moderately controlled diabetic patients with HbA1c values within the range of 6%-8% were selected. The parameters recorded were gingival index, plaque index, sulcus bleeding index, probing pocket depth, clinical attachment level, and HbA1c. The recordings were done at baseline and 6 months after SRP procedures. RESULTS: Reductions in all the clinical parameters were observed and were found to be statistically significant (P < 0.05). CONCLUSION: SRP resulted in a statistically significant reduction in the clinical parameters and HbA1c. Hence, periodontal treatment should be included in the management of diabetic patients.
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Matrix metalloproteinases (MMPs) are the group of enzymes that belong to the family of zinc dependent endopeptidases. These proteases degrade collagen and other important proteins in extracellular matrix (ECM) and regulate cytoskeletal proteins, growth factors, chemokines and cytokines, thereby play significant role during organogenesis and normal tissue turnover. Recent studies highlight the tumorigenic functions of MMPs by modulating tumor microenvironment. Dysregulated MMPs/TIMPs cause an imbalance in crucial cell signals, and lead to serious pathological conditions related to inflammation, uncontrolled cell growth, ECM degradation, increased cell migration, cell death resistance, replicative immortality and the establishment of metastatic niche at secondary sites. Recently established correlation between the higher expression of active MMPs and cancer aggressiveness makes them probable target candidate of cancer diagnosis, prognosis and therapy. The present review focuses on the tumourigenic functions of MMPs and recent advancements in the development of MMP inhibitors of therapeutic potential in cancer treatment.