in this research paper ,researchers found a new therapeutic drug that is SULFASALAZINE for the treatment of neuroblastoma that has a action on SEPIATERIN REDUCTASE
History of DICER1 mutation
DICER1 function
Mutated DICER1 – tumorigenic mechanism
Constellation of lesions associated with DICER1
DICER1 IHC
When to test?
Therapeutic options
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
History of DICER1 mutation
DICER1 function
Mutated DICER1 – tumorigenic mechanism
Constellation of lesions associated with DICER1
DICER1 IHC
When to test?
Therapeutic options
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
TUMORES DE LA CAPA MENINGOTELIAL
SON DEL 13 AL 26% DE LAS NEOPLASIAS INTRACRANEALES
DELECION DEL CROMOSOMA 22q
INMUNOHISTOQUIMICA:
VIM, EMA, CEA, R. Progesterona
MENINGIOMA ATIPICO KI67; 7.2%
MENINGIOMA ANAPLASICO KI 67; 14.7%
KI67 >O IGUAL A 4.2; ALTO
EL HALLAZGO DE INVASION CEREBRAL ES INDICADOR DE RECURRENCIA FRECUENTE (GRADO II OMS).
Audio and slides for this presentation are available on YouTube: http://youtu.be/FyL7sCDc4Zc
Mikael Rinne, MD, PhD, of Dana-Farber Cancer Institute's Center for Neuro-Oncology, discusses the science and genetics behind brain tumors. Rinne covers how scientists can discover DNA alterations in cancer, which alterations are found in brain tumors, and what scientists can do about the alterations.
This talk was originally given at Dana-Farber's "Living with Brain Tumors" forum on Sept. 7, 2013.
For more information, visit the website for Dana-Farber's Center for Neuro-Oncology: http://bit.ly/13nlpEv
“The data presented here and in the literature are consistent with the hypothesis that at least one cancer, retinoblastoma, can be caused by two mutations…. One of these mutations may be inherited as a result of a previous germinal mutation…. Those patients that inherit one mutation develop tumors earlier than do those who develop the nonhereditary form of the disease; in a majority of cases those who inherit a mutation develop more than one tumor.
The treatment for sarcoma cancer is done only through the surgical methods in which the bone and soft-tissue of limb of the patient is saved from extremity tumour cases.
TUMORES DE LA CAPA MENINGOTELIAL
SON DEL 13 AL 26% DE LAS NEOPLASIAS INTRACRANEALES
DELECION DEL CROMOSOMA 22q
INMUNOHISTOQUIMICA:
VIM, EMA, CEA, R. Progesterona
MENINGIOMA ATIPICO KI67; 7.2%
MENINGIOMA ANAPLASICO KI 67; 14.7%
KI67 >O IGUAL A 4.2; ALTO
EL HALLAZGO DE INVASION CEREBRAL ES INDICADOR DE RECURRENCIA FRECUENTE (GRADO II OMS).
Audio and slides for this presentation are available on YouTube: http://youtu.be/FyL7sCDc4Zc
Mikael Rinne, MD, PhD, of Dana-Farber Cancer Institute's Center for Neuro-Oncology, discusses the science and genetics behind brain tumors. Rinne covers how scientists can discover DNA alterations in cancer, which alterations are found in brain tumors, and what scientists can do about the alterations.
This talk was originally given at Dana-Farber's "Living with Brain Tumors" forum on Sept. 7, 2013.
For more information, visit the website for Dana-Farber's Center for Neuro-Oncology: http://bit.ly/13nlpEv
“The data presented here and in the literature are consistent with the hypothesis that at least one cancer, retinoblastoma, can be caused by two mutations…. One of these mutations may be inherited as a result of a previous germinal mutation…. Those patients that inherit one mutation develop tumors earlier than do those who develop the nonhereditary form of the disease; in a majority of cases those who inherit a mutation develop more than one tumor.
The treatment for sarcoma cancer is done only through the surgical methods in which the bone and soft-tissue of limb of the patient is saved from extremity tumour cases.
Sell House Fast Florida, Some Foolproof Home-Selling TacticsJeff Hylands
Selling your house can easily become a stress filled experience — especially when you need to sell it fast. Whatever the reason, don’t panic and not dump your house, but if you follow these tactics,you will get the highest sticker price for your house.
This is the approach our team took to the First Green Bank ethical case.
Internationally recognized for our focus on ethics, Daniels College of Business is proud to present the 12th annual Race & Case Competition. This one-of-a-kind experience marries the intellectual challenge of an ethical business case with the physical test of a downhill NASTAR ski race. Students bring classroom knowledge into the real world by applying critical thinking and innovative practices to a professional, ethical dilemma and then hit the slopes for a day of ambitious, athletic fun!
Zeine Seminar 2010, Cancer Associated Fibroblasts and Microvascular Prolifera...Rana ZEINE, MD, PhD, MBA
World Cancer Congress 2010
Presence of Cancer-Associated Fibroblasts correlates with Microvascular Proliferation which is a Poor Prognostic Factor in Neuroblastoma Tumors
My presentation delivered at the MS Symposium of the Jewish Hospital Berlin (https://www.juedisches-krankenhaus.de/home.html) held on 29 Nar 2023 at the Centrum Judaicum, Oranienburger Strasse, Berlin
Austin Journal of Reproductive Medicine & Infertility is an international scholarly, peer review, Open Access journal, aims to promote the research in Reproductive Medicine that compact with prevention, analysis & management of reproductive problems.
Austin Journal of Reproductive Medicine & Infertility is a comprehensive Open Access peer reviewed scientific journal that covers multidisciplinary fields. We provide limitless access towards accessing our literature hub with colossal range of articles. The journal aims to publish high quality varied article types such as Research, Review, Short Communications, Case Reports, Perspectives (Editorials), Clinical Images.
Austin Journal of Reproductive Medicine & Infertility supports the scientific modernization and enrichment in Reproductive Medicine research community by magnifying access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed member journals under one roof thereby promoting knowledge sharing, collaborative and promotion of multidisciplinary science.
Biofertilizer are microorganisms that help plants to grow by increasing the quantity of nutrients. they defined as preparations containing living cells or latent cells of efficient strains of microorganisms that help crop plants for the uptake of nutrients by their interactions in the rhizosphere.
Biopesticide refers introduction of any living organism such as microorganism including bacteria , fungi , nematodes viruses, protozoa and parasitoids and predators that controls pests by biological non-toxic means e.g. Trichoderma sp., Bacillus thuringiensis, Beauveria etc.
A bioindicator is any an "indicator species" or group of species whose function, population, or status reveal the qualitative status of the environment.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
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This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
1. EFFECT OF SULFASALAZINE ON
HUMAN NEUROBLASTOMA :
ANALYSIS OF SEPIAPTERIN REDUCTASE
AS A NEW THERAPEUTIC TARGET
NAME : RUCHI RANI
ROLL NO. : 20
CLASS : M.Sc BIOTECHNOLOGY, IIIrd SEMESTER
2.
3. NEUROBLASTOMA
Neuroblastoma is an aggressive childhood
malignancy in children upto 5 yr of age.
It is a rare disease in which a solid tumor is
formed by special nerve cells called
neuroblasts
Normally, these immature cells grow and
mature into functioning nerve cells. But in
neuroblastoma, they become cancer cells
instead
NB most commonly starts in the tissue of
the adrenal glands
Like other cancers, NB can metastasize to
other parts of the body, such as the lymph
nodes, skin, liver, and bones
In a few cases, the tendency to get this type
of cancer can be passed down from a parent
to a child (familial type), but most cases of
NB (98%) aren't inherited (sporadic type)
It happens almost exclusively in infants and
children, and is slightly more common in
boys than in girls
4. POLYAMINE
BIOSYNTHESISS
Polyamines are certain biogenic di-, tri-,
and tetra-amines which are derived from
amino acids. In general, the compounds
putrescine, spermine, and spermidine,
sometimes also cadaverine are summarized
as polyamines
By SAMDC
Contribute to cell
migration and
metastasis
Addition of DFMO
Inhibit enzyme ODC
Decrease cell
proliferation
POLYAMINE BIOSYNTHESIS
PA Production
Increases In NB
PA Depletion SPERMIDINE
..
Koomoa DL, Borsics T, Feith DJ, Coleman CC, Wallick CJ,
Gamper I, et al. Inhibition of S- adenosylmethionine decarboxylase
by inhibitor SAM486A connects polyamine metabolism with p53-
Mdm2-Akt/protein kinase B regulation and apoptosis in
neuroblastoma. Mol Cancer Ther. 2009;8(7):2067–75
5. SULFASALAZINE
Sulfasalazine is FDA approved
salicyclate based anti- inflammatory
and immune - modulatory drug
Used to treat bowel inflammation
in patients with ulcerative colitis and
Crohn’s disease and also indicated
for use in rheumatoid arthritis
SSZ identified to inhibit sepiapterin
reductase (SPR) , an enzyme in the
biosynthesis of tetrahydrobiopterin.
From the early research , it is well
known that reduction in SPR
expression significantly reduced
native Ornithine decarboxylase
(ODC) enzyme activity and impeded
the proliferation of NB
They first report the cellular effects of
SSZ on NB tumor cells, due to
inhibition of SPR
They also demonstrate the relevance
of SPR in human NB tumors and
show the combination of SSZ with
DFMO produces synergistic anti-
proliferative effects
SPR
SSZ
6. SPR AND ODC INTERACTION
SPR
ODC
Lange I, Geerts D, Feith DJ, Mocz G, Koster J, Bachmann AS.
Novel interaction of ornithine decarboxylase with sepiapterin
reductase regulates neuroblastoma cell proliferation. J Mol Biol.
2014;426(2):332–46.
8. MAMMALIAN CELL CULTURE
ISOLATION AND CULTURE OF NB CELL LINES-
Isolate human NB cell line SK-N-Be , LAN -5 and SK-N-H
Culture in RPMI medium supplemented with 10% heat inactivated FBS and then mixture
was supplemented with antibiotics
Incubated at 37°C for 3 h
ANALYSIS
WHEN NO SSZ IN CELL CULTURE -
Cell viability assay by formazan
Analysis of SPR mRNA expression in NB by using these parameters :-
A) Age Group
B) MYCN Amplification
C) INSS Stage
SPR –ODC mRNA expression correlation in NB by using these parameters:-
A) Age Group
B) MYCN Amplification
C) INSS Stage
9. ANALYSIS
WHEN SSZ IN CELL CULTURE –
SSZ and DMSO solution were diluted in culture medium and then analysis –
Effect of SSZ on the viability of NB cells lines-
A) SK-N-Be(2)
B) LAN-5
C) SK-N-SH
Synergism of SSZ and DMFO combination treatment in NB cells by using
……….Isobologram analysis
Determination of protein – ligand binding of SSZ to SPR
11. CELL VIABILITY TEST BY FORMAZAN
Figure 1. Cell viability test of NB cell in
……………………. RPMI medium by Formazan.
Figure 2. Cell plate showing NB cell ……
……..Growth in Formazan .
SK-N-Be(2))
SK-N-Be(2)
b
Time
12. ANALYSIS OF SPR mRNA EXPRESSION
Figure 3. SPR mRNA expression
correlation with neuroblastoma clinical
parameters-
a) Age Group
b) MYCN Amplification
c) INSS Stage
13. Spr–odc mrna expression
.
Figure 4. SPR expression correlation with ODC expression in NB : Visual
representation of SPR and ODC expression in NB tumor samples, ranked
horizontally from left to right according to their SPR expression.
14. effect of SSZ ON CELL VIABILITY
Figure 5. Effect of SSZ on the viability of NB cells using the MTS cell viability assay. NB cell
lines SK-N-BE(2)c, SK-N-SH and LAN-5 were treated with increasing concentration of SSZ
for 48 h. Dose dependent inhibition of cell viability was observed.
15. synergism between ssz and dfmo
SK-N-Be(2)c LAN-5
IC50 4.007mM 5.788mM
SK-N-Be(2)c LAN-5
IC50 133.1µM 337.2µM
Figure 6. Analysis for SSZ and DFMO in NB.NB cell lines were used to determine the inhibitory concentration at …
.. which 50% of cells are dead (IC50) after 48h of treatment with –
a) SSZ and b) DFMO
c) Combined cytotoxicity of SSZ and DFMO using the IC50 values from a and b
16. 3D structure of binding of ssz to spr
Figure 7. Binding of SSZ to SPR –
a) SPR dimer front view . Both chains bind SSZ independently;
b) SPR dimer in complex with NADP+;
c) SPR monomer close up front view of the SSZ binding pocket;
d) Overlay view of SSZ and NADP+ binding sites
e) SPR monomer close up front view of the NADP+ binding pocket;
17. .
The results of NB cell experiment show that SSZ has a detrimental effect on
NB cells in in vitro culture and shows synergy with DFMO treatment which is
encouraging
Considering the low toxicity of DFMO and its current use in NB clinical
trials, a combination with the equally low toxic and clinically evaluated SSZ
appears a good lead for future clinical studies
The use of SSZ in combination with DFMO for further experiments, and
possible prioritization as novel therapy for the treatment of NB patients
The identification of the molecular pathways that are activated in response to
SSZ action will need further studies
19. .1)Lange I, Geerts D, Feith DJ, Mocz G, Koster J, Bachmann AS (2014). Novel interaction of ornithine
decarboxylase with sepiapterin reductase regulates neuroblastoma cell proliferation. J Mol Biol.
;426(2):332–46.
2)Cheung NK, Deyer MA.(2013). Neuroblastoma: development biology,cancer genomics and
immunotherapy . Nat Rev Cancer .13(6) : 397-411.
3)Maris JM.(2010).Recent advances in neuroblastoma. N Engl J Med . 362(23):2202-2211.
4)Park JR, Eggert A, Caron H.(2010). Neuroblastoma: biology, prognosis, and treatment. Hematol Oncol
Clin North Am. 24(1): 65-86.
5)Maris JM, Hogarty MD, Bagatell R, Cohn SL.(2007). Neuroblastoma. Lancet. 369(9579):2106-2120.
6)Koomoa DL, Borsics T, Feith DJ, Coleman CC, Wallick CJ, Gamper I, et al (2007). Inhibition of S-
adenosylmethionine decarboxylase by inhibitor SAM486A connects polyamine metabolism with p53-
Mdm2-Akt/protein kinase B regulation and apoptosis in neuroblastoma. Mol Cancer Ther.;8(7):2067–
75.
7) Casero RA Jr, Marton LJ(2007): Targeting polyamine metabolism and function in cancer and other
hyperproliferative diseases. Nat Rev Drug Discov, 6(5):373-390.
20. 8)Plosker GL, Croom KF.(2005). Sulfasalazine: a review of its use in the management of
….rheumatoid arthritis. Aids international ilimited. 65(13):1825-1849. …… ………………..……..
9)Bachmann AS (2004): The role of polyamines in human cancer: prospects for drug combination
…..therapies. Hawaii Med J, 63(12):371-374.………………………………………………………….
10)Brodeur GM.(2003) Neuroblastoba : biological insights into a clinical enigma. Nat Rev Cancer.
…3(3):203-216.………….…………………………………………………………………………..
11)Schwab M, Westermann F, Hero B, Berthold F.(2003) Neuroblastoma : biology and molecular
…….and chromosomal pathology. Lancet Oncol.4(8):472-480.......................……………………....
12)Birnie GG, McLeod TI, Watkinson G.(1981). Incidence of Sulphasalazine–induced male
……infertility. 22:452-470.…………………………………………………………………………….
13)Toovev S, Hudson E, Hendry WF, Levi AJ. (1981) Sulphasalazine and male infertility :
……reversibility and possible mechanism.22: 445-468.……………………………………………...
14)O’Mora’in C, Smethurst P, Dore’CJ, Levi AJ. (1984). Reversible male infertility due to
…….sulphasalazine : studies in man and rat. 25: 1078-1098.……………………………………..