Exploratory analysis of epidemiological and clinicopathological characteristics of soft tissue sarcomas: a single institutional study in Chennai

Background: Soft tissue sarcomas (STS) from mesenchymal origin form diverse and complex group. Gastrointestinal stromal tumors (GIST)s are most common mesenchymal neoplasm of gastrointestinal system. Better comprehension of clinicopathological profile needed to improve overall prognosis. The objective is to study the epidemiological, clinicopathological characteristics, treatment outcome and other prognostic factors predicting overall survival (OS) and progression free survival (PFS) in STS. Methods: This study was conducted in Medical Oncology Department, Govt Royapettah Hospital, Chennai. It is a retrospective study, data retrieved from recorded files of patients with soft tissue sarcomas presented from Jan 2017-Dec 2021, and two years follow up data collected till Dec 2023. Results: In this study 92 patients with soft tissue sarcoma were analysed. Most commonly found histological subtype was GIST (29.3 %). In our study OS rate at 2 years (years) was 0.80. PFS rate at 2 years was 0.70. Surgical status, staging showed correlation with PFS in GIST in cox regression analysis and both PFS, OS in non-GIST sarcomas. In non-GIST sarcomas grade had correlation with PFS and Staging found as an independent factor associated with PFS. Site of primary in GIST and histopathology in non-GIST STS also showed correlation. Conclusions: In this study median OS and PFS not reached till the last date of follow up. Surgical status and staging found to be significant prognostic factors for both GIST and non-GIST sarcomas and grade in non-GIST sarcomas

Effect of oral metronomic chemotherapy on quality of life in advanced or metastatic head and neck cancers

Background: Oral Metronomic chemotherapy (OMCT) is an emerging therapeutic option in advanced/metastatic, head and neck squamous cell carcinoma (HNSCC). It is ideal for frail patients not candidates for platinum-based chemotherapy, and who have minimal response with progressive worsening of quality of life (QOL). To assess the effect of OMCT on changes in quality of life (QOL) in advanced/recurrent HNSCC patients. Methods: Patients with advanced/metastatic recurrent HNSCC, not amenable to radical therapy were included in the study. QOL was assessed with the European organization for research and treatment of cancer (EORTC) QLQ-C30 and QLQ-H&N 35 questionnaires at enrollment and at regular follow up intervals after starting MC. Results: Out of 54 patients, 50 % patients had grade 3 or more pain at enrolment, which improved after OMCT with only 5 % having grade 3 or more pain at 6 months. Mean QLQ-C 30 score at the time of presentation was 68.4. With oral MC, there was a steady increase in QOL score QLQ-C30; 75.35 at 2 months, 81.26 at 4 months, and 85.38 at the end of 6 months. Mean QLQ-H and N 35 score at the time of presentation was 62.50, which gradually improved with oral MC; 71.16 at 2 months, 75.43 at 4 months, and 80.69 at the end of 6 months. Conclusions: The use of oral metronomic therapy with methotrexate, gefitinib and celecoxib significantly improved the QOL and pain control in patients with advanced/recurrent HNSCC

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts

Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast‐like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age‐dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE‐modified extracellular matrix (ECM‐AGEs) showed an AGE‐concentration‐dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM‐AGEs‐treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non‐senescent LECs and contributes to PCO

Peptain-1 blocks ischemia/reperfusion-induced retinal capillary degeneration in mice

IntroductionNeurovascular degeneration results in vascular dysfunction, leakage, ischemia, and structural changes that can lead to significant visual impairment. We previously showed the protective effects of peptain-1, a 20 amino acid peptide derived from the αB-crystallin core domain, on retinal ganglion cells in two animal models of glaucoma. Here, we evaluated the ability of peptain-1 to block apoptosis of human retinal endothelial cells (HRECs) in vitro and retinal capillary degeneration in mice subjected to retinal ischemia/reperfusion (I/R) injury.MethodsHRECs were treated with either peptain-1 or scrambled peptides (200 μg/mL) for 3 h and a combination of proinflammatory cytokines (IFN-γ 20 ng/mL + TNF-α 20 ng/mL+ IL-1β 20 ng/mL) for additional 48 h. Apoptosis was measured with cleaved caspase-3 formation via western blot, and by TUNEL assay. C57BL/6J mice (12 weeks old) were subjected to I/R injury by elevating the intraocular pressure to 120 mmHg for 60 min, followed by reperfusion. Peptain-1 or scrambled peptide (0.5 μg) was intravitreally injected immediately after I/R injury and 7 days later. One microliter of PBS was injected as vehicle control, and animals were euthanized on day 14 post-I/R injury. Retinal capillary degeneration was assessed after enzyme digestion followed by periodic acid–Schiff staining.ResultsOur data showed that peptain-1 entered HRECs and blocked proinflammatory cytokine-mediated apoptosis. Intravitreally administered peptain-1 was distributed throughout the retinal vessels after 4 h. I/R injury caused retinal capillary degeneration. Unlike scrambled peptide, peptain-1 protected capillaries against I/R injury. Additionally, peptain-1 inhibited microglial activation and reduced proinflammatory cytokine levels in the retina following I/R injury.DiscussionOur study suggests that peptain-1 could be used as a therapeutic agent to prevent capillary degeneration and neuroinflammation in retinal ischemia

Tobacco use and caries risk among adolescents - a longitudinal study in Sweden

Background: Smoking and the use of smokeless tobacco have a detrimental impact on general and oral health. The relationship to dental caries is however still unclear. As caries is a multi-factorial disease with clear life-style, socio-economic and socio-demographic gradients, the tobacco use may be a co-variable in this complex rather than a direct etiological factor. Our aim was to analyze the impact of tobacco use on caries incidence among adolescents, with consideration to socio-economic variables by residency, using epidemiological data from a longitudinal study in the region of Halland, Sweden. Methods: The study population consisted of 10,068 adolescents between 16-19 years of age from whom yearly data on caries and tobacco use (cigarette smoking and use of smokeless tobacco) were obtained during the period 2006-2012. Reported DMFS increment between 16 and 19 years of age (Delta DMFS) for an individual was considered as the primary caries outcome. The outcome data were compared for self-reported never vs. ever users of tobacco, with consideration to neighborhood-level socio-economy (4 strata), baseline (i.e., 16 years of age) DMFS and sex. The region consists of 65 parishes with various socio-economic conditions and each study individual was geo-coded with respect to his/her residence parish. Neighborhood (parish-level) socio-economy was assessed by proportion of residing families with low household purchasing power. Results:Delta DMFS differed evidently between ever and never users of tobacco (mean values: 1.8 vs. 1.2; proportion with Delta DMFS > 0: 54.2% vs. 40.5%; p < 0.0001). Significant differences were observed in each neighborhood-level socio-economic stratum. Even after controlling for baseline DMFS and sex, Delta DMFS differed highly significantly between the ever and never users of tobacco (overall p < 0.0001). Conclusion: Tobacco use was clearly associated with increased caries increment during adolescence. Hence, this factor is relevant to consider in the clinical caries risk assessment of the individual patient as well as for community health plans dealing with oral health

Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract

Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice

Background: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury. Methods: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts. Results: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury. Conclusion: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose