Oncological benefits of postoperative radiotherapy in node-negative early stage cancer of the oral cavity with isolated perineural invasion

Perineural invasion has been widely regarded as a poor prognostic factor in cancer of the oral cavity, but adjuvant treatment based only on this is still debatable. We have made an effort to address the question in a retrospective analysis of data from 2009–15 of patients with early node-negative cancers of the oral cavity. Patients with perineural invasion were divided into those who were treated with radiotherapy and those who were not. The records of a total of 169 patients were analysed, and 118 were given adjuvant radiotherapy and 51 were not. The median (range) duration of follow up was 45 (26–86) months. Of 169 patients, 47 (28%) developed recurrence, 28 in the treated, and 19 in the untreated, group. There was a significant disease-free survival benefit for adjuvant treatment (p = 0.047) but no overall survival benefit (p = 0.54).We conclude that adjuvant radiotherapy should be considered for patients with perineural invasion, even in early cancers of the oral cavity.     

Natural killer cells as a promising tool to tackle cancer—A review of sources,methodologies, and potentials

Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies. Among this handful of immune cells of significance, the NK cells stand apart from the rest for not only their direct cytotoxic ability against cancer cells but also their added advantage, which includes their capability of (i) action through both innate and adaptive immune mechanism, (ii) tackling viruses too, giving benefits in conditions where viral infections culminate in cancer, and (iii) destroying cancer stem cells, thereby preventing resistance to chemotherapy and radiotherapy. This review thoroughly analyses the sources of such NK cells, methods for expansion, and the future potentials of taking the in vitro expanded allogeneic NK cells with good cytotoxic ability as a drug for treating cancer and/or viral infection and even as a prophylactic tool for prevention of cancer after initial remission.     

Biomarkers of cardiac injury: an update

Conventional and promising new markers of myocardial injury have become an important diagnostic tool and their prognostic significance is also recognized. In addition, they help identify patients who will derive the most benefit from therapeutic interventions. The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and PubMed Central, the U.S. National Library of Medicine's digital archive of life sciences journal literature (http://www.pubmedcentral.nih.gov/). The data were accessed from books and journals that published relevant articles in this field. The diagnosis of acute myocardial infarction (AMI) has traditionally relied on the combination of chest pain, ECG features, and elevation in serum markers. However, chest symptoms are frequently atypical or absent and ECG changes may be nonspecific or absent. Hence, the diagnosis of acute coronary syndromes has become increasingly dependent on serum markers of cardiac injury. Among them, creatine kinase (CK) is an effective and widely used test, with the recent CKMB assay offering greater specificity and sensitivity. Cardiac troponins facilitate early and rapid diagnosis, enable effective risk stratification in patients with AMI (with or without traditional criteria for MI), and identify those who will benefit from aggressive medical or surgical intervention. Recent data suggest the potential of myoglobin and CKMB isoforms as sensitive markers in the early hours after symptom onset. Cardiac-specific troponins help in rapid diagnosis, prognostication, and treatment of AMI. Troponins also facilitate early detection of recent infarction owing to their prolonged diagnostic window and also aid in the detection of "microinfarction.' CKMB is used to detect reinfarction or infarct extension, if levels rise again after declining. Finally, novel biochemical markers are receiving attention in ongoing trials. They may prove to be more effective in diagnosis and prognosis than their existing counterparts.     

An investigation of vitamin D status in alopecia areata

Alopecia areata (AA) is a type of non-scarring, recurrent patchy loss of hair in hair-bearing areas and is mostly of autoimmune origin. Previous studies have suggested that some autoimmune diseases were found to be associated with vitamin D deficiency. The current study was designed to assess the levels of serum 25-hydroxy vitamin D and C-reactive protein in AA, as compared with controls and to further identify the association between vitamin D levels and disease severity in patients with AA. This cross-sectional study included 45 patients with AA and 45 healthy volunteers. Clinical and anthropometric parameters were recorded, according to a pre-designed proforma. Serum 25-hydroxy vitamin D and high-sensitivity C-reactive protein were estimated using ELISA kits. The severity of AA was determined using Severity of Alopecia Tool (SALT) score. We observed a significant rise in systemic inflammation as seen by elevated high-sensitive C-reactive protein levels and lowered 25-hydroxy vitamin D levels in patients with alopecia areata, compared to controls (p?=?0.001). The levels of 25-hydroxy vitamin D showed a significant negative correlation with disease severity, while hs-CRP levels showed a significant positive correlation with disease severity (ρ?=???0.714, p?=?0.001 and ρ?=?0.818, p?=?0.001). Our results suggest significant systemic inflammation and vitamin D deficiency in alopecia areata, more so with increasing disease severity. This gains particular importance in the treatment of alopecia areata in future, as supplementing vitamin D to AA patients would result in reducing the disease severity and inducing remission.     

Evaluation of Cytopenias Occurring in Imatinib Treated Chronic Myeloid Leukemia (CML) Patients

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008–June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ≥grade 2 anemia, 25 patients with ≥grade 2 neutropenia and 37 patients with ≥grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual’s needs.     

Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective

Atherosclerosis is the root cause of the biggest killer of the 21st century. Mechanisms contributing to atherogenesis are multiple and complex. A number of theories-including the role of dyslipidemia, hypercoagulability, oxidative stress, endothelial dysfunction, and inflammation and infection by certain pathogens-have been propounded from time to time explain this complex phenomenon. Recently it has been suggested that atherosclerosis is a multifactorial, multistep disease that involves chronic inflammation at every step, from initiation to progression, and that all the risk factors contribute to pathogenesis by aggravating the underlying inflammatory process. A better understanding of the pathogenesis of atherosclerosis will aid in devising pharmaceutical and lifestyle modifications for reducing mortality resulting from coronary artery disease (CAD).A comprehensive literature search was conducted using the Web sites of the National Library of Medicine (http:// www.ncbl.nlm.nih.gov/) and PubMed Central, the US National Library of Medicine's digital archive of life sciences literature (http:// www.pubmedcentral.nih.gov/). The data were accessed from books and journals in which relevant articles in this field were published.The whole spectrum of coronary artery disease evolves through various events that lead to the formation and progression of atherosclerotic plaque and finally its complications. Atherosclerosis is the culprit behind coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The pathogenic mechanisms are varied and complex. Of late, the role of lipoprotein (a), homocysteine, and inflammation and infection as prime culprits in pathogenesis of CAD is the subject of intense research and debate. The appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework to understand the clinical benefits of newer therapeutic strategies, and a better understanding of pathogenesis aids in formulating preventive and therapeutic strategies in reducing mortality resulting from CAD.An in-depth knowledge of the various pathogenic mechanisms involved in atherosclerosis can help in substantiating the current existing knowledge about the CAD epidemic. This knowledge will help clinicians to better manage the disease, which affects Indians in its most severe form.     

In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells

Background

Brain tumor-initiating cells (BTICs) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. Oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV) in conventional glioma models but, as seen with other OVs, is only modestly effective for patient-derived BTICs. The objective of this study was to determine whether MyxV treatment against human BTICs could be improved by combining chemotherapeutics and virotherapy.

Methods

A 73-compound library of drug candidates in clinical use or preclinical development was screened to identify compounds that sensitize human BTICs to MyxV treatment in vitro, and synergy was evaluated mathematically in lead compounds using Chou-Talalay analyses. The effects of combination therapy on viral gene expression and viral replication were also assessed.

Results

Eleven compounds that enhance MyxV efficacy were identified, and 6 were shown to synergize with the virus using Chou-Talalay analyses. Four of the synergistic compounds were shown to significantly increase viral gene expression, indicating a potential mechanism for synergy. Three highly synergistic compounds (axitinib, a VEGFR inhibitor; rofecoxib, a cyclooxygenase-2 inhibitor; and pemetrexed, a folate anti-metabolite) belong to classes of compounds that have not been previously shown to synergize with oncolytic viruses in vitro.

Conclusions

This study has identified multiple novel drug candidates that synergistically improve MyxV efficacy in a preclinical BTIC glioma model.     

Relationship of raised serum total and protein bound sialic acid levels with hyperinsulinemia and indices of insulin sensitivity and insulin resistance in non-diabetic normotensive obese subjects

AimsObesity is known to be associated with cardiovascular disease and interaction between inflammation and insulin resistance is reported to enhance the cardiovascular risk in these subjects. The present study was designed to assess indices of insulin sensitivity, insulin resistance and sialic acid levels and their association in non-diabetic normotensives obese subjects.Materials and methodsThe present study was conducted in 30 obese male subjects and results were compared with 30 subjects with normal body weight. Insulin, total sialic acid and protein bound sialic acid were estimated in all the subjects. Insulin resistance was calculated by using Homeostatic Model Assessment-insulin resistance formula. Insulin sensitivity was assessed by quantitative insulin check index and insulin sensitivity index.ResultsInsulin resistance, serum total and protein bound sialic acid levels were significantly increased in obese cases as compared to non-obese controls. Total sialic acid showed significant positive correlation with HOMA-IR (p < 0.01), BMI (p < 0.01), waist and hip circumference (p < 0.01) and negative correlation with QUICKI (p < 0.01) and insulin sensitivity index (p = 0.018). There was no significant correlation between protein bound sialic acid and indices of insulin resistance and insulin sensitivity.ConclusionSialic acid levels are elevated in obese subjects and its association with insulin resistance and reduced insulin sensitivity may enhance the cardiovascular risk in these subjects.