Concurrent chemoradiation and Tumor Treating Fields (TTFields, 200 kHz) for patients with newly diagnosed glioblastoma: patterns of progression in a single institution pilot study.

Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We conducted a pilot clinical trial of concurrent chemoradiation with TTFields and report pattern of progression. MATERIALS AND METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from the primary enhancing lesion. RESULTS: Thirty patients were enrolled on the trial. Twenty were male with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 15.2 months (1.7-23.6 months). Ten (33.3%) patients had a methylated promoter status. Twenty-seven patients (90%) had progression, with median PFS of 9.3 months (range 8.5 to 11.6 months). Six patients presented with distant recurrence, with median distance from primary lesion of 5.05 cm (2.26-6.95 cm). One infratentorial progression was noted. CONCLUSIONS: We observed improved local control using concurrent chemoradiation with TTFields for patients with newly diagnosed when compared to historical controls. Further data are needed to validate this finding. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03477110.

A phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCL.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.

Long-Term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. METHODS: This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). CONCLUSIONS: Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity.

Prevalence of chronic kidney disease in patients undergoing cardiac rhythm device removal.

Cardiac implantable electronic device (CIED) leads can cause central venous stenosis (CVS). In addition, these devices can get infected. Both are critically important considerations in patients with chronic kidney disease (CKD) for at least two reasons: (i) central veins serve as the final pathway should these patients need an arteriovenous access to provide dialysis therapy; and (ii) the presence of renal failure increases the risk of CIED infection. In this analysis, we investigated the prevalence as well as the degree of chronic kidney disease in patients harboring a CIED. Patients undergoing CIED removal were evaluated from 2001 to 2011. The patients were categorized into CKD stage I-V based on National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. A total of 503 patients underwent CIED removal. Demographic characteristics revealed that 30% had hypertension, 44% were diabetics, 77% had coronary artery disease, and 84% suffered from congestive heart failure. Ninety percent (452/503) of the patients had CKD (stage I = I9 [4.2%], stage II = 189 [41.8%], stage III A = 96 [21.2%], stage III B = 59 [13.0%], stage IV = 45 [9.9%], and stage V = 44 [9.7%]). Overall, 148 (32.7%) patients (stage III B, stage IV, and stage V) of 452 had advanced renal failure. The results of this study reveal that one-third of CIED patients undergoing device removal have advanced chronic kidney disease.

Biodegradation of low density polyethylene (LDPE) by mesophilic fungus 'Penicillium citrinum' isolated from soils of plastic waste dump yard, Bhopal, India.

Low density Polyethylene (LDPE) in various forms has become a part of life. Its accretion due to non degradable nature is concern, endangering life on earth. Amongst various methods of LDPE disposal bioremediation is regarded as ecofriendly & widely accepted. Current investigation was an attempt to isolate potent PE degrading fungus from municipal landfill soils of Bhopal, India loaded with plastic waste.16 fungal isolates were recorded from the site; PE deteriorating fungus was screened using mineral salt agar medium amended with 3% LDPE powder as sole carbon source. The isolate Penicillium citrinum showed fast fungal colony growth in screening medium was selected for biodegradation study. P.citrinum showed 38.82 ± 1.08% weight loss of untreated LDPE pieces; to improve the degradation capacity nitric acid pretreatment was performed; biodegradation was significantly stimulated by 47.22 ± 2.04% after it's pretreatment. Laccase, lipase, esterase & manganese peroxidase activities were assayed by spectrophotometer. LDPE biodegradation was analyzed by weight loss %, change in pH during fungal growth, field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FTIR) & thermogravimetric analysis (TGA). FTIR spectra showed appearance of new functional groups assigned to hydrocarbon biodegradation, confirming enzymatic role in process. Changes in FTIR spectra of LDPE samples (untreated & pretreated) before & after biodegradation & surface changes in the biodegraded LDPE (indicated from FE-SEM) confirmed depolymerization of LDPE. Further changes in thermal decomposition rates of biodegraded samples in comparison to control, validate biodegradation. This is the first report signifying high competence of P.citrinum in LDPE degradation without prior pretreatment.

Case report: durable response of gliomatosis cerebri with concurrent tumor-treating fields (TTFields) and chemoradiotherapy treatment.

BACKGROUND: Gliomatosis cerebri (GC) is a rare and aggressive form of widely disseminated glioma infiltrating at least 3 lobes of the brain. It is a diffuse pattern of growth seen in glioma rather than a distinct pathological diagnosis based on new Word Health Organization (WHO) classification. Despite this, it is associated with worse prognosis than equally graded gliomas. Tumor treating fields (TTFields) treatment is a more recent advancement in glioma treatment delivered through low energy, intermediate frequency (200 kHz) electromagnetic fields, with multi-modal mechanisms of action. It is Food and Drug Administration (FDA) approved for newly diagnosed and recurrent glioblastoma (GBM). The aim of this case report is to present a durable response of GBM associated GC to concurrent TTFields with chemoradiation. CASE DESCRIPTION: We report a 64-year-old male with left parietal GBM, IDH wild type, WHO grade 4 with extensive GC change. After resection of the enhancing lesion, the patient received concurrent tumor-treating fields (TTFields) with radiation and temozolomide, enrolled in SPARE trial (NCT03477110). The patient had a rapid response in the areas of gliomatosis change demonstrated on the magnetic resonance imaging 1 month post-radiation treatment. The response of GC was durable. His glioma recurred 11 months after surgery with new enhancing lesions, treated with radiosurgery. He had further extensive progression of enhancing lesions 13 months after surgery, and received bevacizumab treatment. The patient ultimately passed away 17 months after surgery. Despite progression of enhancing lesions, the GC changes remained controlled. He also had favorable progression-free survival of 11 months and overall survival of 17 months. CONCLUSIONS: This case serves as an example of how combination TTFields with chemoradiation may elicit a durable response of GC in patients with GBM.

On the role of histamine receptors in regulating pigmentary responses in Oreochromis mossambicus melanophores.

PURPOSE: The present work was carried out to reveal the involvement of histamine receptors at the neuro-melanophore junction of teleost, Oreochromis mossambicus. METHODS: The isolated scale melanophores were assayed using the mean melanophore size index and their responses were recorded in presence of various concentrations of histamine along with H(1) and H(2) receptor specific agonists and antagonist and potentiator compound 48/80. RESULTS: Melanophores showed high sensitivity to histamine and its specific agonists. Histamine caused a dose-dependent pigment aggregation, whereas 2-(2-Pyridyl) ethylamine (PEA), a specific H(1)R agonist also caused aggregation in a similar manner. Conversely, amthamine, a specific H(2)R agonist resulted in pigment dispersion. The effects were antagonized by mepyramine; specific H(1)R antagonist and ranitidine a specific H(2)R antagonist. CONCLUSION: It is concluded that O. mossambicus melanophores have both H(1) and H(2) receptors which mediate melanophore aggregation and dispersion respectively. Compound 48/80 augmented the melanin-aggregating and dispersing effects of PEA and amthamine. It is suggested that the effect of histamine is directly mediated through H1 and H2 receptors, whereas H1Rs may be predominantly involved in the aggregatory responses.

Insights into the physiomodulatory role of histaminergic receptors in vertebrate skin pigmentation.

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from unique distribution of pigments throughout the body. Being the largest organ of the body, skin is always under the influence of internal and external factors that often react to certain intrinsic agents in an unorthodox manner, modifying the integral pigmentation patterns and resulting into complex physiological aberrancies. One of these intrinsic agents involved in numerous immunological and non-immunological processes within the body is histamine. Histamine mediates its multifarious biological activities stimulated by various immunological and non-immunological stimuli via differential expression of its four classes of receptors (H1, H2, H3, and H4) on effector cells. Interestingly, recent studies have described the expression of functional histamine receptors in vertebrate pigment cells melanocytes, emphasizing the potential physiomodulatory effects of this molecule in the phenomenon of skin pigmentation. This noteworthy finding has opened numerous perspectives to elucidate several contentions regarding skin-related conditions. The focus of this review is to provide an updated overview of the involvement and role of histamine and its receptors together with the physiological and pharmacological aspects of their agonists and antagonists impinging the phenomenon of pigmentation and the mechanisms by which they do so.

In vitro responses of fish melanophores to lyophilized extracts of Psoralea corylifolia seeds and pure psoralen.

CONTEXT: Psoralens are naturally occurring furanocumarins used in photochemotherapy of several skin diseases. They are obtained from dried ripe fruits of Psoralea corylifolia Linn. (Fabaceae). However, little research has been done to study the melanogenic activity of P. corylifolia seeds and their active ingredients on the pigment cells, the melanophores taking account of their cholinergic activity. OBJECTIVE: The present work was carried out to determine the effects of lyophilized seed extracts of P. corylifolia, along with pure psoralen on the isolated scale melanophores of Channa punctatus Bloch. (Channidae), which are a disguised type of smooth muscle cells and offer excellent in vitro opportunities for studying the effects of drugs. MATERIALS AND METHODS: Effects of lyophilized extracts of P. corylifolia and pure psoralen were studied on the isolated scale melanophores of C. punctatus as per the modified method of Bhattacharya et al. (1976) . RESULTS: The lyophilized extract of P. corylifolia and its active ingredient psoralen caused significant melanin dispersal responses leading to darkening of the fish scale melanophores, which were completely antagonized by atropine and hyoscine. These melanin dispersal effects were also found to be markedly potentiated by neostigmine, an anticholinesterase agent. DISCUSSION: In the present study, the lyophilized extract of P. corylifolia seeds and standard psoralen in different dose ranges induced powerful melanin dispersal effects of the previously adrenaline-aggregated isolated scale melanophores of C. punctatus. Comparatively, psoralen caused a more sustained and powerful melanin dispersal within the isolated fish melanophores and interestingly the concentrations required to achieve maximal dispersion of melanophore were 10 times less than that of lyophilized seed extract of P. corylifolia. The physiologically significant dose-related melanin dispersion effects of lyophilized P. corylifolia seeds and synthetic psoralen per se were found to be completely abolished by atropine and hyoscine, which are specific cholino-muscarinic receptor blockers. These data strongly indicate that in the fish C. punctatus, the dispersion of melanin granules within the scale melanophores is mediated by choline receptors of muscarinic nature. CONCLUSION: It appears that the melanin dispersal effects of the extracts of P. corylifolia and pure psoralen leading to skin darkening are mediated by cholino-muscarinic- or cholino-psoralen-like receptors having similar properties.

A Pilot Trial Using Telemedicine in Radiation Oncology: The Future of Health Care Is Virtual.

Background: Social determinants of health directly affect cancer survival. Driven by advances in technology and recent demands due to COVID-19, telemedicine has the ability to improve patient access to care, lower health care costs, and increase workflow efficiency. The role of telemedicine in radiation oncology is not established. Materials and Methods: We conducted an IRB-approved pilot trial using a telehealth platform for the first post-radiation visit in patients with any cancer diagnosis. The primary endpoint was feasibility of using telehealth defined by completion of five telehealth visits per month in a single department. Secondary endpoints included the ability to assess patients appropriately, patient and physician satisfaction. Physicians were surveyed again during the pandemic to determine whether viewpoints changed. Results: Between May 27, 2016 and August 1, 2018, 37 patients were enrolled in the Telehealth in Post-operative Radiation Therapy (TelePORT) trial, with 24 evaluable patients who completed their scheduled telehealth visit. On average, 1.4 patients were accrued per month. All patients were satisfied with their care, had enough time with their physician and 85.7% believed the telehealth communication was excellent. All physicians were able to accurately assess the patient's symptoms via telehealth, whereas 82.3% felt they could accurately assess treatment-related toxicity. Physicians assessing skin toxicity from breast radiation were those who did not feel they were able to assess toxicity. Discussion and Conclusions: Both health care providers and patients have identified telemedicine as a suitable platform for radiation oncology visits. Although there are limitations, telemedicine has significant potential for increasing access of cancer care delivery in radiation oncology.

A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial.

Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473.

Target treatment with stereotactic radiation for recurrent gliomas.

High grade gliomas (HGG) have a propensity to recur locally and have poor outcomes. As such, safe and effective treatment is paramount. Target treatment with stereotactic radiation allows safe re-irradiation through minimizing normal brain tissue radiation due to its high precision. In this review, we evaluated the clinical experiences using SRS and FSRT for re-irradiation in HGG. We report the radiobiological advantages and disadvantages of both modalities as well as the safety and efficacy published in current literature.

Purified Mushroom Tyrosinase Induced Melanogenic Protein Expression in B16F10 Melanocytes: A Quantitative Densitometric Analysis.

BACKGROUND: Human skin exists in a wide range of different colors and gradations, ranging from white to brown to black. This is due to the presence of a chemically inert and stable pigment known as melanin, which is produced deep inside the skin but is displayed as a mosaic at the surface of the body. METHODS & MATERIALS: In mammalian melanocytes, melanosome is a highly specialized organelle where melanin is synthesized. Melanin synthesis is controlled by tyrosinase, the vital enzyme in melanogenic pathway. The present investigation is based on the effect of purified tyrosinase of Agaricus bisporus on B16F10 melanocytes for melanogenic protein expression. RESULTS: After the treatment of purified tyrosinase B16F10 melanocytes did not show any cytotoxic effect. Melanin content in B16F10 melanocytes was increased by purified tyrosinase in a dose-dependent manner. Quantitative western blot analysis revealed that cellular tyrosinase intensity was enhanced after treatment with purified tyrosinase for 48 hours, where the band intensity had a steady increase in the absorption of purified tyrosinase in B16F10 cells. The density analysis described increased absorption for 2 to 5 bands as 2.7, 3.7, 6.7 and 8.6% respectively. The bands in the comparative analysis of western blot were between the Rf value range (0.40-0.57) with maximum absorption of 3000 intensity curve at 32µg/mL, rather than higher concentration 64µg/mL, showing a decrease in the absorption. CONCLUSION: It is presumed that purified tyrosinase can be used as contestants for the treatment of vitiligous skin conditions.

Links between the Prophet Muhammad (PBUH) recommended foods and disease management: A review in the light of modern superfoods.

Nutrition and other bioactive natural products present in specific foods within a balanced diet play an indispensable role in maintaining and promoting human health. Plants are rich sources of a balanced nutrition because of high content of bioactive products; hence, most of them recently have acquired the status of superfoods. It has been used since ancient times for the treatment of various ailments, and these traditional medicines still remain as one of the most affordable and easily accessible sources of treatment in the primary health-care system. The scientifically based use of these superfoods date back to the era of Prophet Muhammad along with other historical uses of plant products. Prescription of a large number of herbal foods such as dates, pomegranate, olives, figs, grapes, and black seeds was successfully proposed by him. These recently have become superfoods with their powerful healing properties and act as favorable dietary interventions for disease prevention as well as for the good maintenance of health. The use of these foods as ingredients of natural origin with fewer side effects seems to be more favorable than the chemical treatment, which is often complicated. The present review is an attempt to provide a brief survey of the literature on scientifically based significance of these superfoods carried out by various researchers and exploration of a wide spectrum of their pharmacological actions which include antidiabetic, anticancer, immune modulator, analgesic, anti-inflammatory, and hepatoprotective properties.

Melanogenic effect of purified mushroom tyrosinase on B16F10 Melanocytes: A Phase Contrast and Immunofluorescence Microscopic Study.

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. It has been proven that tyrosinase plays a pivotal role in melanocytes dendrite formation; however, the molecular mechanism underlying this process has not been fully elucidated. The morphological changes were observed under a phase contrast microscope. These changes were evident, with globular cell bodies and increased numbers of tree branch-like dendrites. The present work aimed to study the morphoanatomic effects of purified tyrosinase to determine its skin-darkening potential using B16F10 melanocyte, which has not been done to date. Phase contrast and immunofluorescence microscopic analysis of B16F10 melanocytes has been done after treatment with various concentrations of purified tyrosinase along with standard tyrosinase (Sigma) in order to explore the mechanism of action of purified tyrosinase induced skin darkening. The phase contrast microscopic results showed that the number of melanocytes with melanin-loaded dendrites has increased significantly in purified tyrosinase treated cells in a dose dependent manner leading to skin darkening. In addition, immunofluorescence microscopic analysis revealed purified tyrosinase increase cellular tyrosinase expression in doze dependent manner due to tyrosinase absorption in B16F10 melanocyte. Present findings proved that purified tyrosinase possesses a skin darkening potential and could be used as a safe melanogenic agent for the treatment of hypopigmentation disorders or vitiligo.

Recent Updates in Melanocyte Function: The Use of Promising Bioactive Compounds for the Treatment of Hypopigmentary Disorders.

BACKGROUND: Skin pigmentation is a broadly appearing phenomenon in nature which plays an important task of determining the appearance and biology of all vertebrates including human beings. Skin color is a crucial attribute, determined by the synthesis of melanin pigment within melanocytes by the process of melanogenesis and is regulated by many extrinsic as well as intrinsic factors. Tyrosinase catalyzes the key step of melanogenesis, dysfunction of tyrosinase leads to reduce melanin production which results in severe clinical and aesthetical problems of hypopigmentation. Therefore, the regulation of melanin production is an important strategy in the treatment of abnormal skin pigmentation for cosmetic and medicinal purpose. METHOD: The present review covers the various aspects of mammalian melanocyte biology which will help in the identification of key regulators of melanogenesis from pharmaceutical and pharmacological point of view. Further sections of the review focus on the dysfunctions of melanogenic pathways, which result in severe clinical and aesthetical problems of hypopigmentation. CONCLUSION: We have also attempted to highlight the ability of available scientifically validated plant extracts to naturally enhance melanin synthesis in order to cure hypopigmentation.

Effect of Purified Mushroom Tyrosinase on Melanin Content and Melanogenic Protein Expression.

In mammalian melanocytes, melanosome is a highly specialized organelle where melanin is synthesized. Melanin synthesis is controlled by tyrosinase, the vital enzyme in melanogenic pathway. The present investigation is based on an effect of purified mushroom tyrosinase of Agaricus bisporus on B16F10 melanocytes for the melanin production via blocking pigment cell machinery. Using B16F10 melanocytes showed that the stimulation of melanogenesis by purified tyrosinase is due to increased tyrosinase absorption. Cellular tyrosinase activity and melanin content in B16F10 melanocytes were increased by purified tyrosinase in a dose-dependent manner. Western blot analysis revealed that cellular tyrosinase levels were enhanced after treatment with purified tyrosinase for 48 hours. Furthermore, tyrosinase induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner. The purified tyrosinase-mediated increase of tyrosinase activity was significantly attenuated by H89, LY294002, Ro-32-0432, and PD98059, cAMP-dependent protein kinase inhibitors. The results indicate that purified tyrosinase can be used as contestant for the treatment of vitiligous skin conditions.

Microbial tyrosinases: promising enzymes for pharmaceutical, food bioprocessing, and environmental industry.

Tyrosinase is a natural enzyme and is often purified to only a low degree and it is involved in a variety of functions which mainly catalyse the o-hydroxylation of monophenols into their corresponding o-diphenols and the oxidation of o-diphenols to o-quinones using molecular oxygen, which then polymerizes to form brown or black pigments. The synthesis of o-diphenols is a potentially valuable catalytic ability and thus tyrosinase has attracted a lot of attention with respect to industrial applications. In environmental technology it is used for the detoxification of phenol-containing wastewaters and contaminated soils, as biosensors for phenol monitoring, and for the production of L-DOPA in pharmaceutical industries, and is also used in cosmetic and food industries as important catalytic enzyme. Melanin pigment synthesized by tyrosinase has found applications for protection against radiation cation exchangers, drug carriers, antioxidants, antiviral agents, or immunogen. The recombinant V. spinosum tryosinase protein can be used to produce tailor-made melanin and other polyphenolic materials using various phenols and catechols as starting materials. This review compiles the recent data on biochemical and molecular properties of microbial tyrosinases, underlining their importance in the industrial use of these enzymes. After that, their most promising applications in pharmaceutical, food processing, and environmental fields are presented.