Treatment Pattern and Outcomes in Verrucous Carcinoma of Oral Cavity: A Single Institutional Retrospective Analysis from a Tertiary Cancer Center and Review of Literature.

Verrucous carcinoma (VC) is a locally invasive uncommon histopathological variant of oral squamous cell cancer. There is paucity of literature regarding control rates in these cases. We intend to report the outcomes in terms of administered treatment and control rates. 28 patients of oral cavity verrucous carcinomas treated at our institute from March 2014 to December 2018 were reviewed retrospectively. Demographic profile, histopathological features and clinical outcomes were analyzed. Statistical analysis was performed with SPSS for Mac (version 23.0). Median age was 54 years (range 31-75) with M:F ratio of 25:3. Buccal mucosa was the most common site. All patients underwent surgical resection except one. Of these, 24 had neck dissection; 12 had supra-omohyoid neck dissection, eleven had modified neck dissection and one patient underwent radical neck dissection. Three patients had their histology upgraded to squamous cell carcinomas in the post-operative histopathology. The post-operative staging was as follows: 21% stage I and 35% stage II. One patient opted for non-surgical approach and received radical concurrent chemoradiotherapy. Median follow up was 12 months (range 6-36). Two patients had local failures and one had a regional failure. No distant metastasis was found. There was one death. 14-Months survival rate was 92%. Estimated 18 month loco-regional control rate was 92%. Curative surgical resection remains the cornerstone for VC of oral cavity. Any change of histopathology post-operatively to squamous cell carcinoma is a poor prognostic sign and needs appropriate adjuvant treatment.

Belowground fungal volatiles perception in okra (Abelmoschus esculentus) facilitates plant growth under biotic stress.

Microbial volatile organic compounds (mVOCs) have great potential in plant ecophysiology, yet the role of belowground VOCs in plant stress management remains largely obscure. Analysis of biocontrol producing VOCs into the soil allow detailed insight into their interaction with soil borne pathogens for plant disease management. A root interaction trial was set up to evaluate the effects of VOCs released from Trichoderma viride BHU-V2 on soil-inhabiting fungal pathogen and okra plant growth. VOCs released into soil by T. viride BHU-V2 inhibited the growth of collar rot pathogen, Sclerotium rolfsii. Okra plants responded to VOCs by increasing the root growth (lateral roots) and total biomass content. VOCs exposure increased defense mechanism in okra plants by inducing different enzyme activities i.e. chitinase (0.89 fold), ß-1,3-glucanase (0.42 fold), peroxidase (0.29 fold), polyphenol oxidase (0.33 fold) and phenylalanine lyase (0.7 fold) when inoculated with S. rolfsii. In addition, T. viride BHU-V2 secreted VOCs reduced lipid peroxidation and cell death in okra plants under pathogen inoculated condition. GC/MS analysis of VOCs blend revealed that T. viride BHU-V2 produced more number of antifungal compounds in soil medium as compared to standard medium. Based on the above observations it is concluded that okra plant roots perceive VOCs secreted by T. viride BHU-V2 into soil that involved in induction of plant defense system against S. rolfsii. In an ecological context, the findings reveal that belowground microbial VOCs may play an important role in stress signaling mechanism to interact with plants.

Seed biopriming with antagonistic microbes and ascorbic acid induce resistance in tomato against Fusarium wilt.

Seed biopriming is an emerging technique to enhance seed germination under stress conditions. An integrated approach of tomato seed biopriming with ascorbic acid, Trichoderma asperellum BHU P-1 and Ochrobactrum sp. BHU PB-1 was applied to observe the response against wilt pathogen of tomato Fusarium oxysporum f. sp. lycopersici (FOL). Tomato seeds bioprimed with the aforementioned application expressed augmented seed germination and activated of defense response. Seed germination was recorded higher (80 %) at low concentration (1 pM) of ascorbic acid as compared to high concentration of 1 mM (41 %). Combination of both ascorbic acid and antagonistic microbe treatments (T5 & T6) significantly reduced disease incidence (up to 28 %) in tomato plants at 10 days. T5 and T6 treated plants exhibited higher accumulation of total phenol content and increased activity of Phenylammonia lyase (PAL), Peroxidase (PO), Chitinase (Chi) and Polyphenol oxidase (PPO) as compared to control (T1) plants. ROS formation in the form of H2O2 was also found to be reduced in combined treatment. Histochemical analysis revealed that phenylpropanoid pathway (lignin deposition) was more activated in combined priming treatment plants as compared to individual treatment upon challenge inoculation with FOL. Transcript expression analysis of defense genes confirmed the up-regulation of PAL (2.1 fold), Chi (0.92 fold), Pathogenesis related proteins (PR) (1.58 fold) and Lipoxygenase (Lox) (0.72 fold) in T6 treatment as compared to T1 treatment plants at 96 h. This study reveals that ascorbic acid treatment with antagonistic microbes through seed priming effectively induced seed germination and elicited defense mechanism to control wilt disease in tomato plants.

Sphingobacterium sp. BHU-AV3 Induces Salt Tolerance in Tomato by Enhancing Antioxidant Activities and Energy Metabolism.

Salt tolerant bacteria can be helpful in improving a plant's tolerance to salinity. Although plant-bacteria interactions in response to salt stress have been characterized, the precise molecular mechanisms by which bacterial inoculation alleviates salt stress in plants are still poorly explored. In the present study, we aimed to determine the role of a salt-tolerant plant growth-promoting rhizobacteria (PGPR) Sphingobacterium BHU-AV3 for improving salt tolerance in tomato through investigating the physiological responses of tomato roots and leaves under salinity stress. Tomato plants inoculated with BHU-AV3 and challenged with 200 mM NaCl exhibited less senescence, positively correlated with the maintenance of ion balance, lowered reactive oxygen species (ROS), and increased proline content compared to the non-inoculated plants. BHU-AV3-inoculated plant leaves were less affected by oxidative stress, as evident from a reduction in superoxide contents, cell death, and lipid peroxidation. The reduction in ROS level was associated with the increased antioxidant enzyme activities along with multiple-isoform expression [peroxidase (POD), polyphenol oxidase (PPO), and superoxide dismutase (SOD)] in plant roots. Additionally, BHU-AV3 inoculation induced the expression of proteins involved in (i) energy production [ATP synthase], (ii) carbohydrate metabolism (enolase), (iii) thiamine biosynthesis protein, (iv) translation protein (elongation factor 1 alpha), and the antioxidant defense system (catalase) in tomato roots. These findings have provided insight into the molecular mechanisms of bacteria-mediated alleviation of salt stress in plants. From the study, we can conclude that BHU-AV3 inoculation effectively induces antioxidant systems and energy metabolism in tomato roots, which leads to whole plant protection during salt stress through induced systemic tolerance.

Correlation of Molecular Markers in High Grade Gliomas with Response to Chemo-Radiation.

BACKGROUND: The standard of care in high grade glioma (HGG) is maximal safe surgical resection followed by adjuvant radiotherapy (RT) with/without chemotherapy. For anaplastic gliomas, studies have shown use of procarbazine, lomustine, vincristine (PCV) improves overall survival (OS) and progression free survival (PFS). Currently, there is substantial evidence that molecular markers strongly predict prognosis and response to treatment. METHODS: Between January 2016 to January 2018, 42 patients were accrued and followed up till April 2019. The primary end points were to correlate molecular markers with response to therapy in terms of OS and PFS in HGG. The secondary end point was to evaluate frequency of 1p/19q codeletion, IDH 1 mutation, ATRX deletion and p53 in HGG patients. RESULTS: The median age was 46 years (range 18-67) with M:F ratio 30:12. The frequency of IDH1 mutation,1p/19q codeletion, p53 mutation and ATRX mutation were 42.8%, 16.6%, 42.8% and 14.2% respectively. All the seven patients with 1p/19q codeletion had IDH1 mutation. Median follow up was 22 months. The 20-months PFS for different mutations were as follows; IDH1-mutated vs wild type: 53.6% vs 29.8%; p-0.035, 1p/19q codeleted vs non-codeleted: 85.7% vs 62.3%; p-0.011, p53 wild type vs mutated 32.1% vs 35.6%; p-0.035 and ATRX lost vs retained: 55.6% vs 53.3%; p- 0.369. The 20-months OS for IDH1 mutated vs wild type: 82.4% vs 30.6%; p-0.014, 1p/19q codeleted vs non-codeleted: 85.7% vs 65.8%; p-0.104, p53 wild-type vs mutated 45.5% vs 73.9%; p-0.036 and ATRX lost vs retained: 100% vs 60.3%; p-0.087. CONCLUSION: Codeletion of 1p/19q with IDH1 mutation in HGG is associated with a significantly favourable PFS. However, larger studies with longer follow up are required to evaluate OS and PFS in all the molecular subgroups.

Trichoderma asperellum T42 induces local defense against Xanthomonas oryzae pv. oryzae under nitrate and ammonium nutrients in tobacco.

Trichoderma has been explored and found to play a vital role in the defense mechanism of plants. However, its effects on host disease management in the presence of N nutrients remains elusive. The present study aimed to assess the latent effects of Trichoderma asperellum T42 on oxidative burst-mediated defense mechanisms against Xanthomonas oryzae pv. oryzae (Xoo) in tobacco plants fed 10 mM NO3 - and 3 mM NH4 + nutrients. The nitrate-fed tobacco plants displayed an increased HR when Xoo infected, which was enhanced in the Trichoderma-treated plants. This mechanism was enhanced by the involvement of Trichoderma, which elicited NO production and enhanced the expression pattern of NO-modulating genes (NR, NOA and ARC). The real-time NO fluorescence intensity was alleviated in the NH4 +-fed tobacco plants compared to that fed NO3 - nutrient, suggesting the significant role of Trichoderma-elicited NO. The nitrite content and NR activity demonstration further confirmed that nitrate metabolism led to NO generation. The production of ROS (H2O2) in the plant leaves well-corroborated that the disease resistance was mediated through the oxidative burst mechanism. Nitrate application resulted in greater ROS production compared to NH4 + nutrient after Xoo infection at 12 h post-infection (hpi). Additionally, the mechanism of enhanced plant defense under NO3 - and NH4 + nutrients mediated by Trichoderma involved NO, ROS production and induction of PR1a MEK3 and antioxidant enzyme transcription level. Moreover, the use of sodium nitroprusside (100 µM) with Xoo suspension in the leaves matched the disease resistance mediated via NO burst. Altogether, this study provides novel insights into the fundamental mechanism behind the role of Trichoderma in the activation of plant defense against non-host pathogens under N nutrients.

Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade: phytoblockers of metastasis cascade.

Cancer metastasis is a multistep process in which a cancer cell spreads from the site of the primary lesion, passes through the circulatory system, and establishes a secondary tumor at a new nonadjacent organ or part. Inhibition of cancer progression by dietary phytochemicals (DPs) offers significant promise for reducing the incidence and mortality of cancer. Consumption of DPs in the diet has been linked to a decrease in the rate of metastatic cancer in a number of preclinical animal models and human epidemiological studies. DPs have been reported to modulate the numerous biological events including epigenetic events (noncoding micro-RNAs, histone modification, and DNA methylation) and multiple signaling transduction pathways (Wnt/ß-catenin, Notch, Sonic hedgehog, COX-2, EGFR, MAPK-ERK, JAK-STAT, Akt/PI3K/mTOR, NF-κB, AP-1, etc.), which can play a key role in regulation of metastasis cascade. Extensive studies have also been performed to determine the molecular mechanisms underlying antimetastatic activity of DPs, with results indicating that these DPs have significant inhibitory activity at nearly every step of the metastatic cascade. DPs have anticancer effects by inducing apoptosis and by inhibiting cell growth, migration, invasion, and angiogenesis. Growing evidence has also shown that these natural agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways. In this review, we discuss the variety of molecular mechanisms by which DPs regulate metastatic cascade and highlight the potentials of these DPs as promising therapeutic inhibitors of cancer.

Modulation of nutritional and antioxidant potential of seeds and pericarp of pea pods treated with microbial consortium.

Microbial populations have diverse roles within rhizosphere where interactions among distinct microorganisms along with the host may lead to mutualistic associations. The present study aimed to investigate the nutritional and antioxidant qualities of seeds and pericarp of pea raised from seeds treated with beneficial microbes namely Bacillus subtilis BHHU100, Trichoderma harzianum TNHU27 and Pseudomonas aeruginosa PJHU15 either singly and/or in consortia. A significant increase in total phenolic, flavonoid, ascorbic acid and protein contents, free radical scavenging activity, hydroxyl radical scavenging activity, iron chelation and reducing power were observed in the seeds and pericarp of pods treated with a consortium of microbes in comparison to control pods. Also, the differential accumulation of phenolic compounds, namely, shikimic acid, gallic acid, tannic acid, syringic acid, p-coumaric acid, quercetin and kaempferol, was observed from the HPLC chromatogram of the seed extracts of different treatments. We especially emphasized on dietary importance of the pod pericarp, other than seeds, along with their modulation by microbial consortium. The study also highlights the role of beneficial microbes in improving nutritional value by providing protection against oxidative stress.

Compatible rhizosphere microbes mediated alleviation of biotic stress in chickpea through enhanced antioxidant and phenylpropanoid activities.

The study was conducted to examine efficacy of a rhizospheric microbial consortium comprising of a fluorescent Pseudomonas (PHU094), Trichoderma (THU0816) and Rhizobium (RL091) strain on activation of physiological defense responses in chickpea against biotic stress caused by the collar rot pathogen Sclerotium rolfsii. Results of individual microbes were compared with dual and triple strain mixture treatments with reduced microbial load (1/2 and 1/3rd, respectively, of individual microbial load compared to single microbe application) in the mixtures. Periodical studies revealed maximum activities of phenylalanine ammonia lyase [E.C. 4.1.3.5] and polyphenol oxidase [E.C. 1.14.18.1] and accumulation of total phenol content in chickpea in the triple microbe consortium treated plants challenged with the pathogen compared to the single microbe and dual microbial consortia. Similarly, the expression of the antioxidant enzymes superoxide dismutase [E.C.1.15.1.1] and peroxidase [E.C.1.11.1.7] was also highest in the triple microbial consortium which was correlated with lesser lipid peroxidation in chickpea under the biotic stress. Histochemical staining clearly showed maximum and uniform lignification in vascular bundles of chickpea stem sections treated with the triple microbes. The physiological responses were directly correlated with the mortality rate as least plant mortality was recorded in the triple microbe consortium treated plants. The results thus suggest an augmented elicitation of stress response in chickpea under S. rolfsii stress by the triple microbial consortium in a synergistic manner under reduced microbial load.

Induction of plant defense enzymes and phenolics by treatment with plant growth-promoting rhizobacteria Serratia marcescens NBRI1213.

In greenhouse experiments, plant growth-promoting rhizobacteria (PGPR) Serratia marcescens NBRI1213 was evaluated for plant growth promotion and biologic control of foot and root rot of betelvine caused by Phytophthora nicotianae. Bacterization of betelvine (Piper betle L.) cuttings with S. marcescens NBRI1213 induced phenylalanine ammonia-lyase, peroxidase, and polyphenoloxidase activities in leaf and root. Qualitative and quantitative estimation of phenolic compounds was done through high-performance liquid chromatography (HPLC) in leaf and root of betelvine after treatment with S. marcescens NBRI1213 and infection by P. nicotianae. Major phenolics detected were gallic, protocatechuic, chlorogenic, caffeic, ferulic, and ellagic acids by comparison of their retention time with standards through HPLC. In all of the treated plants, synthesis of phenolic compounds was enhanced compared with control. Maximum accumulation of phenolics was increased in S. marcescens NBRI1213-treated plants infected with P. nicotianae. In a greenhouse test, bacterization using S. marcescens NBRI1213 decreased the number of diseased plants compared with nonbacterized controls. There were significant growth increases in shoot length, shoot dry weight, root length, and root dry weight, averaging 81%, 68%, 152%, and 290%, respectively, greater than untreated controls. This is the first report of PGPR-mediated induction of phenolics for biologic control and their probable role in protecting betelvine against P. nicotianae, an important soil-borne phytopathogenic fungus.