Enhancing quality assurance in radiotherapy for gynaecological cancers: implementation of an on-demand peer review process.

OBJECTIVES: Ensuring high-quality radiotherapy requires peer-reviewing target volumes. The Royal College of Radiologists recommends peer review specifically for individual target volumes in cases of gynaecological cancers. This study presents the outcomes of implementing an on-demand peer review system for gynaecological cancers within our institute. METHODS: The peer review process was planned for gynaecological cancer cases intended for curative radiotherapy. After junior clinical oncologists (COs) completed the segmentation, two senior COs specializing in gynaecological cancers conducted the peer review. All peer review outcomes were recorded prospectively. The audit process compliance, the proportion of patients requiring major and minor modifications in target volumes, the direction of changes, and the factors influencing these changes were reported. RESULTS: A total of 230 patients were eligible, and out of these, 204 (88.3%) patients underwent at least one peer review. Among the patients, 108 required major modifications in their target volumes. P-charts revealed a stabilization in the need for major modifications at the end of three months, indicating that 38.2% and 28% of patients still required major modifications for the nodal and primary CTV, respectively. Multivariable analysis demonstrated that major modifications were associated with the use of extended field radiotherapy and radical radiation in non-cervical primary cases. CONCLUSIONS: An on-demand peer review system was feasible and resulted in clinically meaningful, major modifications in the target volumes for 53% of patients. ADVANCES IN KNOWLEDGE: Gynaecological cancers require ongoing peer review to ensure quality of care in radiotherapy. A flexible on-demand system not only ensures that patient treatment start is not delayed but also has an important educational role for junior trainees.

Conversion of amino-terephthalonitriles to multi-substituted single benzene fluorophores with utility in bioimaging.

Substitution of two fluorine atoms of the tetrafluoroterephthalonitrile (TFTN) ring (ortho to each other) by amine nucleophiles through SNAr chemistry is achievable. However, tri- and tetra-substitution towards multi-substituted single benzene fluorophores (SBFs) is harder due to increased electron richness of the TFTN moiety. Tertiary amine donors promote the molecule towards such multi-substitution guided by the steric obstruction to intramolecular charge transfer to the TFTN ring. Contrarily, secondary amine substituents with better lone pair donation to the TFTN ring cannot induce the SNAr pathway and instead promote hydrolysis of the nitrile groups of the TFTN moiety. Theoretical investigations have helped unearth the reasons for this observed difference in chemical reactivities and also explain the differences in the emission spectra. Finally, the success of the synthetic method towards multi-substitution is showcased through creation of a highly lipophilic SBF bearing an octyl unit and demonstrating its utility in in vitro cellular imaging.

Single Institution Experience of Postoperative Electron Beam Radiation Therapy in the Treatment of Keloids.

PURPOSE: Surgical excision followed by postoperative radiation therapy is an accepted modality to prevent keloid recurrence. Our practice has been to use electron beam radiation postoperatively to prevent recurrence, and we share our experience with this method in this study. METHODS AND MATERIALS: Twenty-two patients with 40 keloids treated postoperatively with electron beam radiation at our institution from 2014 to 2019 were analyzed retrospectively. Electron beam radiation was used for treatment in all cases, and radiation was initiated within 24 hours of surgery. A dose of 20 Gy in 5 fractions was delivered to the postoperative scar in 95% of the sites, and 8 Gy to 10 Gy in a single fraction was delivered to the remaining 5%. The patients were followed up, and recurrences were documented. RESULTS: At a mean follow-up of 35 months (range, 7-66 months), local control and cosmesis were achieved in 90% (36 of 40) of the treated sites with electron beam radiation therapy delivered at a dose of 20 Gy in 5 fractions. All recurrent keloids were located on the anterior chest wall over the sternum. There was no difference in outcome based on age, sex, or keloid length. CONCLUSIONS: Electron beam radiation therapy is a feasible, convenient, and safe modality for postoperative treatment of keloids. It achieves excellent local control with no grade 3 or higher toxicities.

Effect of low- and high-level groundwater arsenic on peripheral blood and lung function of exposed rural women.

The World Health Organization (WHO) recommended maximum contaminant level (MCL) of arsenic (As) in drinking water at 10 µg/L. Many Asian countries still have their MCL for As at 50 µg/L. The current cross sectional study was conducted on asymptomatic females (without As related skin lesions) selected from rural areas of West Bengal, Baruipur and Dhamakhali [low As 11-50 µg/L; N,93]; Kamardanga & Sibhati [high As>50 µg/L; N,70] and Boria [Control; As<10 µg/L N,118] of West Bengal, India. The study was designed to compare the status of peripheral blood and lung function due to prolonged As exposure. The lung function parameters were considered according to Miller's prediction quadrant - FVC less than 80% indicated restrictive lung, FEV1/FVC less than 70% showed obstructive lung and both FVC and FEV1/FVC less than predicted percentage exhibited combined lung function decrement. The study showed that groundwater As concentration [22.5 ± 19.2 (low), 67.8 ± 26.9 (high) and 1.02 ± 2.3 µg/L (control)] was correlated with nail As content of the enrolled women. Linear regression depicted that nail As content influenced reduction of haemoglobin (ß: 0.43; 95%CI: 0.02 to -0.006; p = 0.0001) and CD56+ NK cells (ß: 0.53; 95%CI: 0.07 to -0.03; p = 0.0001) per 1 µg/g increase in As in nails. Multivariate logistic regression exhibited that nail As content was associated with reduction of lung function parameters [FEV1 (Exp B:1.04; 95%CI: 1.022 to 1.055; p = 0.0001) and FVC (Exp B:1.05; 95%CI: 1.03 to 1.07; p = 0.0001) per 1 µg/g increase in As in nails. Hence the study may be indicative of the fact that even in asymptomatic women, increase in chronic As exposure may weaken immune surveillance and provoke respiratory ailments.

Arsenal of Phytochemicals to Combat Against Arsenic-Induced Mitochondrial Stress and Cancer.

Significance: Phytochemicals are important dietary constituents with antioxidant properties. They affect various signaling pathways involved in the overall maintenance of interior milieu of the cell. Arsenic, an environmental toxicant, is well known for its deleterious consequences, such as various diseases, including cancers in humans. Mitochondria are the cell's powerhouse that fuel all metabolic energy requirements. Dysfunctional mitochondria due to stressors may lead to abnormal functioning of the organelle, hampering the crucial cellular cross talks and ultimately leading to cancer. Application of phytochemicals against arsenic-induced mitochondrial disorders may be a preventive measure to counteract the ruinous impacts of the metalloid. Recent Advances: In recent years, extensive research on the role of mitochondria in cancer gives a better understanding of the areas the organelle covers in maintaining a healthy cell or in inducing carcinogenicity. Detailed knowledge of the mitochondrial governances would enable researchers to administer numerous phytochemicals to ameliorate altered oxidative phosphorylation, mitochondrial membrane potential (MMP), mitochondrial oxidative stress, unfolded protein response, glycolysis, or even apoptosis. Critical Issues: In this review, we have addressed how various phytochemicals belonging to diverse classes combat against arsenic-induced mitochondrial oxidative stress, depletion of MMP, cell cycle abrogation, apoptosis, glycolytic damages, oncogenic regulations, chaperones, mitochondrial complexes, and mitochondrial membrane pore formation in both in vitro and in vivo models. Future Directions: Insightful application of mitoprotective phytochemicals against arsenic-induced mitochondrial oxidative stress and carcinogenesis may guide researchers to develop preclinical chemopreventive agents to fight arsenic toxicity in humans.

Dietary phytochemicals in the regulation of epithelial to mesenchymal transition and associated enzymes: A promising anticancer therapeutic approach.

Epithelial to mesenchymal transition (EMT) is a biological phenomenon that plays a primordial role for initiation of metastasis. It renders cancer cells with increased self-renewal and tumor-initiating capabilities and exacerbated resistance to apoptosis and chemotherapy. Hence, regulation of EMT stands out to be an important strategy in controlling the behavior of malignant cells. Despite the enormous amount of preclinical data on the implication of EMT in cancer progression, there is still lack of routine clinical translation at therapeutic levels. The need of EMT-modulating drugs with high efficacy and low cytotoxicity has led to studies involving the evaluation of the efficacy of a plethora of various classes of phytochemicals present in dietary sources of fruits and vegetables. This review summarizes the role of these different classes of phytochemicals, their natural/synthetic analogs, and their nano-formulations in regulation of EMT in various preclinical models through attenuation of primary signaling pathways. Numerous proteins, transcription factors and enzymes targeted by various classes of phytochemicals in repression of EMT has been presented in this review. Additionally, we have critically analyzed the existing literature and provided views on new direction for accelerating the discovery of novel drug candidates which could be cautiously administered without concomitant effects.

Epigallocatechin-3-gallate partially restored redox homeostasis in arsenite-stressed keratinocytes.

Arsenite (AsIII) is known for inducing severe oxidative stress and skin carcinogenesis. Contrastingly, phytochemical, epigallocatechin-3-gallate (EGCG) combats toxic insults. Our study focused on the effect of EGCG on redox status of AsIII-stressed normal human keratinocytes, HaCaT cells. EGCG (50 µm) increased the cell viability by 29% in AsIII (50 µm) insulted HaCaT cells but exhibited pro-oxidant activity by elevated expression of the oxidative stress markers. EGCG was effective not only in reducing AsIII-induced nuclear expression of Nrf2 and Nrf2Ser40 but also in increasing nuclear expression of Keap1 both at protein and mRNA level. EGCG did not have similar effects on all Nrf2 downstream targets. EGCG elevated expression of HO-1 and γ-GCL,showed no change in MRP1 but decreased superoxide dismutase, NAD(P)H dehydrogenase quinone 1 and glutathione S transferase activity in AsIII-treated HaCaT cells. EGCG along with AsIII caused decreased phosphorylation of Nrf2 at ser40 residue, which might have facilitated Keap1-mediated nuclear export and degradation of Nrf2 and paved the pro-survival signal for AsIII-insulted HaCaT cells. In conclusion, it might be indicated that EGCG in spite of inducing the pro-oxidant effect was effective in increasing the viability of AsIII-treated HaCaT cells by partially restoring the Nrf2/Keap1-mediated signaling axis.

Sensitization to silk allergen among workers of silk filatures in India: a comparative study.

BACKGROUND: Sericulture plays an eminent role in development of rural economy in India. Silk filature is a unit where silk is unwound from the cocoons and the strands are collected into skeins. During the process workers are exposed to the high molecular weight proteins like Sericin and Fibroin which are potent allergens leading to sensitization over a period of time and subsequently occupational related health disorders. OBJECTIVE: To identify and compare the magnitude of silk allergen sensitization in workers of silk filatures. METHODS: A community based comparative descriptive study was conducted for a period of 1 year at Ramanagara in south India. One hundred twenty subjects working in the silk filatures formed the study group. For comparison, 2 types of controls were selected viz.120 subjects who were not working in the silk filatures but resided in the same geographical area (control A) and 360 subjects who were not working in silk filatures as well not residing in the same geographical area (control B). Skin prick test was used to identify the silk allergen sensitization. RESULTS: Mean age was 34.14 ± 2.84 years in the study group. Mean age was 40.59 ± 14.40 years and 38.54 ± 12.20 years in control A and control B, respectively. There were 35 males (29.16%) and 85 females (70.84%) in the study group. There were 58 (48.34%) males and 62 (51.66%) females and 152 (42.2%) males and 208 females (57.8%) in control A and control B, respectively. Sensitization to silk allergen was 35.83% in the study group and 20.83% in the control group A and 11.11% in control group B. There was difference in the allergen sensitivity between the study group and control groups and it was statistically significant (chi-square = 38.08; p < 0.001). CONCLUSION: There is high burden of silk allergen sensitization among silk filature workers.

Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research.

A study on occupational asthma among workers of silk filatures in South India.

BACKGROUND: The production of silk is a multidimensional and multistep process involving exposure of workers to allergens at work place. The silk allergen has been implicated in the development of bronchial asthma. OBJECTIVES: To identify the prevalence of occupational asthma (OA) and to identify sensitization to silk allergen and among workers in silk filature units. MATERIALS AND METHODS: A community-based cross-sectional study was conducted in silk filature units of Ramanagara (Silk City) in Karnataka, South India, for a period of 6 months. One hundred and twenty workers of silk filature units who met the inclusion and exclusion criteria were recruited into the study group. For comparison, a control group comprising of 120 individuals not working in silk filature units was constituted. All the subjects were interviewed using the standardized International Union against Tuberculosis and Lung Diseases (IUATLD) Questionnaire and subjected to the skin prick test, which used the extracts of silk allergen. RESULTS: The study group comprised of 35 males and 85 females, whereas the control group comprised of 58 males and 62 females. The prevalence of occupational asthma among workers in silk filatures was 20.83%. It was observed that 35.83% of those in the study group and 20.83% of those in the control group were found to be sensitive to silk allergen. This difference was statistically significant (χ(2)= 6.64; P < 0.05). CONCLUSION: There is a high burden of sensitization to silk allergen and occupational asthma among silk filature workers in South India.

Biogeographic and evolutionary implications of a diverse paleobiota in amber from the early Eocene of India.

For nearly 100 million years, the India subcontinent drifted from Gondwana until its collision with Asia some 50 Ma, during which time the landmass presumably evolved a highly endemic biota. Recent excavations of rich outcrops of 50-52-million-year-old amber with diverse inclusions from the Cambay Shale of Gujarat, western India address this issue. Cambay amber occurs in lignitic and muddy sediments concentrated by near-shore chenier systems; its chemistry and the anatomy of associated fossil wood indicates a definitive source of Dipterocarpaceae. The amber is very partially polymerized and readily dissolves in organic solvents, thus allowing extraction of whole insects whose cuticle retains microscopic fidelity. Fourteen orders and more than 55 families and 100 species of arthropod inclusions have been discovered thus far, which have affinities to taxa from the Eocene of northern Europe, to the Recent of Australasia, and the Miocene to Recent of tropical America. Thus, India just prior to or immediately following contact shows little biological insularity. A significant diversity of eusocial insects are fossilized, including corbiculate bees, rhinotermitid termites, and modern subfamilies of ants (Formicidae), groups that apparently radiated during the contemporaneous Early Eocene Climatic Optimum or just prior to it during the Paleocene-Eocene Thermal Maximum. Cambay amber preserves a uniquely diverse and early biota of a modern-type of broad-leaf tropical forest, revealing 50 Ma of stasis and change in biological communities of the dipterocarp primary forests that dominate southeastern Asia today.