The Communion of Saints: Christian and Tamil Saiva Perspectives

Discussions on saints normally focus on the nature and meaning of sainthood. While apostels, church fathers, martyrs and people of outstanding dedication are considered as saints in Christian tradition, the Vedic sages and gurus are taken as counterparts in the Hindu religious tradition. But mostly significance is attached to their individual worth, charisma and exemplary life. However, the communion of saints is a significant phenomenon in the New Testament and its resemblance seems to lie more in the wandering saints of the regional bhakti traditions of Hinduism (C-500-700 CE) than in the Vedic sages and gurus. Particularly the theological significance attached to the communion of saints in the Tamil Saiva scriptures is remarkable. Although the canonical leaders or teachers of Saivism (nayanars) are well acknowledged for their devotional experience and their contribution to Saiva Siddhanta, the theological significance of the communion of saints remains an undeveloped theme

Lessons from a clinicopathological study of breast cancer

Background: It is estimated for every two new breast cancer cases diagnosed, one breast cancer death is reported in India. It is important regional variations in disease behaviour and health care delivery are studied to understand the elevated mortality of breast cancer in India.Methods: In this retrospective study, 198 patient records were scrutinized for breast cancer related demographic data, disease related information, treatment and pathological data.Results: The median age at presentation was 52 years. The results replicated national trends with regards to menopausal status, menarche, parity and breast feeding. Low parity and age at presentation had a strong inverse correlation (P<0.001). EBC (61%) was the commonest with LABC (28%) and Metastatic disease (13.6%) also prevalent. HR positive (47%) molecular type was the commonest with HER 2 neu (30%) and TNBC (22%) types also noted. Core biopsy was the preferred diagnostic test. Metastatic work up had a yield of 13.6%. Mastectomy was the only surgery procedure; none had BCS or sentinel node biopsy. Surgery done by surgical oncologist had better oncological outcomes.Conclusions: Epidemiological profile of breast cancer in south India confirms to national trends. BCS and sentinel node biopsy are considered standard of care in breast cancer care however seems unavailable in government funded hospitals in south India

Validation of control genes and a standardised protocol for quantifying gene expression in the livers of C57BL/6 and ApoE−/− mice

The liver plays a critical role in food and drug metabolism and detoxification and accordingly influences systemic body homeostasis in health and disease. While the C57BL/6 and ApoE−/− mouse models are widely used to study gene expression changes in liver disease and metabolism, currently there are no validated stably expressed endogenous genes in these models, neither is it known how gene expression varies within and across liver lobes. Here we show regional variations in the expression of Ywhaz, Gak, Gapdh, Hmbs and Act-β endogenous genes across a liver lobe; Using homogeneous samples from the four liver lobes of 6 C57BL/6 mice we tested the stability of 12 endogenous genes and show that Act-β and Eif2-α are the most stably expressed endogenous genes in all four lobes and demonstrate lobular differences in the expression of Abca1 cholesterol efflux gene. These results suggest that sampling from a specified homogeneous powdered liver lobe is paramount in enhancing data reliability and reproducibility. The stability of the 12 endogenous genes was further tested using homogeneous samples of left liver lobes from 20 ApoE−/− mice on standard or high polyphenol diets. Act-β and Ywhaz are suitable endogenous genes for gene expression normalisation in this mouse model

Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodeling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice. This study shows that reduced KLF2 signaling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.</p> <p>Methods</p> <p>To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.</p> <p>Results</p> <p>Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (<it>P </it>= 0.041), increased lymph node metastasis (<it>P </it>= 0.001), less differentiation (<it>P </it>= 0.005), increased recurrence (<it>P </it>= 0.038) and shorter survival (<it>P </it>= 0.004) of the patients.</p> <p>Conclusion</p> <p>In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.</p

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Variability in Surgical Quality among Surgeons in Breast Cancer Surgery Keywords

Abstract Introduction: Quality assurance is an essential aspect of cancer care. Assessment of surgical quality in breast cancer is still evolving. Variability in surgical care among surgeons has been well documented in literature and we sought to investigate such variation between two groups of surgeons referring patients to our oncology center. Methods: A prospective review of patient records of all breast cancer referrals to our department was made. Two groups were identified and segregated based on the performance of mastectomy by a general surgeon (GS) or by a surgical oncologist (SO). Patients treated with modified radical mastectomy for clinical stages 1 -3 were included for the study. Patient demographic data and disease related information were collected in addition to thorough evaluation of the surgical pathology report. Margin positivity, mean nodal harvest, nodal ratio, inadequate axillary clearance, revision surgery and the use of radiotherapy for inadequate nodal dissection were the parameters evaluated in the study. Results: A total of 142 patient records were evaluated 72 designated as group 1 (general surgeons) and 70 as group 2 (surgical oncologist). The median age was 52 years and both groups were evenly balanced for age, laterality of breast lesion, histological type and grade. The mean nodal harvest was 8 vs. 14 nodes, and significant differences were observed in favor of surgical oncology group in margin positivity (P = 0.01), inadequate axillary clearance (P = 0.0001), and requirement of radiotherapy for inadequate axillary clearance (P = 0.0001) but not for revision surgery (P = 0.134). An assessment of prognostic factors revealed both groups to be well balanced for confounding factors. Conclusion: Breast cancer surgical care is amenable to quality assessment. Variation in oncological clearance exists between surgical oncologist and non-oncology trained surgeons involved in mastectomy for breast cancer. An assessment of factors leading to the observed quality differences may be addressed in future trials to ensure optimal breast cancer care

Lessons from a clinicopathological study of breast cancer

Background: It is estimated for every two new breast cancer cases diagnosed, one breast cancer death is reported in India. It is important regional variations in disease behaviour and health care delivery are studied to understand the elevated mortality of breast cancer in India.Methods: In this retrospective study, 198 patient records were scrutinized for breast cancer related demographic data, disease related information, treatment and pathological data.Results: The median age at presentation was 52 years. The results replicated national trends with regards to menopausal status, menarche, parity and breast feeding. Low parity and age at presentation had a strong inverse correlation (P&lt;0.001). EBC (61%) was the commonest with LABC (28%) and Metastatic disease (13.6%) also prevalent. HR positive (47%) molecular type was the commonest with HER 2 neu (30%) and TNBC (22%) types also noted. Core biopsy was the preferred diagnostic test. Metastatic work up had a yield of 13.6%. Mastectomy was the only surgery procedure; none had BCS or sentinel node biopsy. Surgery done by surgical oncologist had better oncological outcomes.Conclusions: Epidemiological profile of breast cancer in south India confirms to national trends. BCS and sentinel node biopsy are considered standard of care in breast cancer care however seems unavailable in government funded hospitals in south India

Loss of keratin 8 phosphorylation leads to increased tumor progression and correlates with clinico-pathological parameters of OSCC patients.

BACKGROUND: Keratins are cytoplasmic intermediate filament proteins expressed in tissue specific and differentiation dependent manner. Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression, invasion and poor prognosis in human oral squamous cell carcinomas (OSCCs). K8 and K18 undergo several post-translational modifications including phosphorylation, which are known to regulate their functions in various cellular processes. Although, K8 and K18 phosphorylation is known to regulate cell cycle, cell growth and apoptosis, its significance in cell migration and/or neoplastic progression is largely unknown. In the present study we have investigated the role of K8 phosphorylation in cell migration and/or neoplastic progression in OSCC. METHODOLOGY AND PRINCIPAL FINDINGS: To understand the role of K8 phosphorylation in neoplastic progression of OSCC, shRNA-resistant K8 phospho-mutants of Ser73 and Ser431 were overexpressed in K8-knockdown human AW13516 cells (derived from SCC of tongue; generated previously). Wound healing assays and tumor growth in NOD-SCID mice were performed to analyze the cell motility and tumorigenicity respectively in overexpressed clones. The overexpressed K8 phospho-mutants clones showed significant increase in cell migration and tumorigenicity as compared with K8 wild type clones. Furthermore, loss of K8 Ser73 and Ser431 phosphorylation was also observed in human OSCC tissues analyzed by immunohistochemistry, where their dephosphorylation significantly correlated with size, lymph node metastasis and stage of the tumor. CONCLUSION AND SIGNIFICANCE: Our results provide first evidence of a potential role of K8 phosphorylation in cell migration and/or tumorigenicity in OSCC. Moreover, correlation studies of K8 dephosphorylation with clinico-pathological parameters of OSCC patients also suggest its possible use in prognostication of human OSCC