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You can use this link to learn more about this program: https://catalog.uwm.edu/nursing/sustainable-peaceb… This is my resume too. 
 In the statement:Explain your reasons for pursuing graduate study;Describe specific interests and your background in the field;List any relevant skills or training you have acquired;List relevant academic awards or honors you have received.Sabaa Haleem Abdulrazzaq
(920) 509-1876
SUMMARY
Friendly, open, respectful, and self-motivated. Very responsible, result- orientated, with excellent
problem-solving skills. Able to work independently and as a team player.
VOLUNTEER EXPERIENCE
PHARMACY VOLUNTEER, MERCY MEDICAL CENTER
APRIL 2015- JANUARY 2017
Assist pharmacist by sending medication to room using sender machine. Make new medication
orders. Load medication onto carts.
CHILDREN’S TEACHER, BOYS AND GIRLS CLUB
JULY 2016- JUNE 2017
Help kids do their own homework those are at Elementary School.
WORK EXPERIENCE
CHILD CARE ASSISTANT, JORDAN RIVER FOUNDATION
SEPTEMBER 2010-FEBRUARY 2011
Ensured safety of children in the Youth for Change program. Encouraged diversity and cultural
understanding.
PHARMACY TECHNICIAN, NAGIOS
AUGUST 2013-MARCH 2014
Assisted pharmacist to fill orders. Completed customer orders in person and over the phone.
Accepted orders from delivery service. Maintained and balanced cash register daily. Oversaw
weight, height, and BMI machine.
REFUGEE GUIDE, WORLD RELIEF
OCTOBER 2014-MARCH 2015
Packed and prepared boxes of necessities for the refugee families. Distributed clothing and other
needs to newly arriving refugees
INTERPRETER, FOX VALLEY COMMUNICATIONS
JUNE 2016- OCTOBER 2016
Interprets for clients of Affinity Health Care system over the phone and in-person during
appointments and for general communication. Arabic/ English and English/Arabic.
RECORD THE POWERPOINT, WCLC
Record the voice to Interpreter from English to Arabic to let the students understand what the
rule of the classes to learn English.
RESIDENT ASSISTANTS, THE FOX VILLAGE STUDENTS’ APARTMENT
FEBRUARY 2018- DECEMBER 2018
I used to work in the office, arrange the boxes, send the information to the residents that we
would like to inform them, organize events each month, and highlight the facts and explain the
conditions of residence or in a more precise law to the students resident in the section, answer
calls and emails; leave a message to the director if necessary, also give the visitor a tour to get
people to know the building.
SUPER DESK, UW MILWAUKEE HOUSING- KENILWORTH
MAY 2021- NOVEMBER 2021
I work as a Front Desk and Security Service, my job working more to help the residents as
Professors, graduate, and undergraduate students. Also, international students. Answer the phone
call. Assistant the students and their parents, answer them question especially on move-in time
when students came from another state. Writing IR reports.
TEACHER ASSISTANCE 4K, YMCA
AUGUST 2022- PRESENT
Being around the kids teach them subjects would help to develop the brain in the right growth
way and make sure they know how to ask, when, and where. Prepare them for the next step to
start one new school system.
LEADER TEACHER, BOYS & GIRLS CLUB
SEPTEMBER 2022- PRESENT
Leading the behavior of students after the official school period. Trying to spend their energy on
entertainment and educational matters at the same time. Guiding them to the extent of respect for
this study period and respect for teachers and monitoring their behavior with students and during
the school period.
RESEARCH SPECIALIST, UNIVERSITY OF WISCONSIN OSHKOSH
NOVEMBER 2022-PRESENT
Worked in the Biology department (Parasite) under supervision of Dr. Michelle Michalski on the
necessary research to build a colony of mosquitoes and obtain worms. Researched what happens
from infecting the gerbils with worms. Attended training for Read Animal Care Manual, Animal
Care and Use Training, Disaster Plan, N-95, Whistle Blower’s Policy, and Daily Room Checks &
Abnormal Clinical Signs. Did some tests from CITI like: Working with Gerbils in Research
Settings, Aseptic surgery, Post-Procedural Care: Minimizing Pain and Distress, Working with
IACUC.
EDUCATION
AL QUDS COLLEGE AMMAN, JORDAN
2012-2013
Degree: Medical Assistant (Pharmaceutics).
UW OF MILWAUKEE
SPRING 2019- SPRING 2022
Degree: Biochemistry Major with Clinical Pharmacology Option
LANGUAGES
Arabic and English
Abdulrazzaq 1
Sabaa Abdulrazzaq
Dr. Surerus, Kristene
Chemistry 691- 010
Tamoxifen
Abdulrazzaq 2
Tamoxifen is an anti-estrogen-based drug that has been recommended for endocrine breast
cancer therapy by the World Health Organization for more than 25 years. The drug is produced
commercially using a two-stage process catalyzed by palladium nanoparticles. The two stages
are the direct and cross-coupling of commercially available compounds resulting in an
economical process. It is used in combination with RNA nanoparticles which reduce the
proliferation, metastasis, and development of breast cancer cells hence making them susceptible
to the drug. The use of coupled tamoxifen and NLC medication has proved to overcome the
issues which have been associated with the sole use of tamoxifen treatment. Systemic toxicity
which is a common side effect of anticancer drugs reduced and hepatotoxicity was absent. This
mode of delivery has so far proved to be the best as it has been shown to improve the efficacy of
the drug whilst overcoming the toxicity issues associated with anticancer treatment.
According to Lorns et al. 2009, just like any other drug, breast cancer cells have become resistant
to tamoxifen. They put forward that reducing the resistance of breast cancer cells to this
treatment requires further research. In their research, several inhibitors responsible for cancer cell
inhibition were studied for their contribution to fighting cancer and their potential for cancer
therapy. These inhibitors included the PDK1 (Phospho Dependent Kinase 1), Protein Kinase b,
S6 kinase, and Mammalian Target of Rapamycin (mTOR) inhibitors. These scientists’ focus was
on how the blocking of the PDK1 pathway would help in reducing the resistance of breast cancer
cells to tamoxifen.
The article outlines direct and cross-coupling stage procedures which they use to manufacture
tamoxifen. Diphenylacetylenes undergo direct carbolithiation after which they are cross coupled
with a highly selective alkenyl lithium reagent in the ratio of 10:1 resulting in a high yield of
Tamoxifen. The catalyst used is the palladium nanoparticle, a highly active metal catalyst.
Abdulrazzaq 3
The use of synthetic methods to produce drugs is a notably great trend in the pharmacological
industry as it results in high yields operating at lower temperatures and low raw products,
especially with the use of transition metals as catalysts. However, this new trend has its perks
which include longer reaction times, the release of poisonous wastes, and a, decrease in cost
efficiency. The issue of time and temperatures has been handled by direct coupling of reagents.
Direct cross-coupling which would be the savior and shortcut in terms of solving all these
current issues has not been proved possible yet. Therefore, despite the synthetic production of
anticancer drugs being a bright idea, it is yet to be polished considering its unsolved drawbacks
(Heijnen et al., 2019).
Figure (1) above is an illustration of how tamoxifen, a highly active and important
pharmaceutical with (possible) applications in the treatment of a range of disorders, especially
breast cancer in this case. The alkyl–ether substituent usually consisting of an amine, (blue) and
Abdulrazzaq 4
para phenylene functionality (red), as well as the alkyl fragment (green) on the remaining alkene
position, demonstrate structural differences in the triphenylethylene scaffold.
A variety of syntheses for (Z)-tamoxifen have been described due to their medical relevance
(Fig. 2). The McMurry coupling of two ketones is a well-known method for the synthesis of
(hindered) alkenes, and it can construct the alkene fragment in tamoxifen using reagents 1 and 2.
Alternatively, 1, 2-addition of ketone 3 with Grignard reagent 4 followed by elimination yielding
an alkene is a viable option; however, both isomers (E/Z) are frequently isolated using this
method. The alkenyl–boronic acid/ester, or organozinc reagent 5, is obtained by transmetallation
of the lithium intermediate formed by carbolithation of the equivalent acetylene. Cross-coupling
these reagents with bromide 6 gives a plausible pathway to the final medication. However,
transmetallation results in additional synthetic stages and/or stoichiometric waste. As a result,
direct coupling of the alkenyl lithium reagent 7, which is produced via carbolithiation of
diphenylacetylene, is a valuable atom efficient alternative to these procedures (Heijnen et al.,
2019).
Abdulrazzaq 5
Heijnen et al., 2019 compared their process to other (recently) reported tamoxifen synthesis
processes as theirs produced this drug in good yield and with less waste which is LiBr in the last
step). Comparison considered the atom economy and the Reaction Mass Efficiency (RME).
Figure 3 below, depicts a wide range in atom economy (blue) amongst multiple reported
tamoxifen syntheses. The technique published by LaRock in 2005 is the closest to the process
investigated by Heijnen et al., 2019 with the atom economy being 48 vs. 67 respectively.
However, LaRock’s process resulted in excess reagents generating a poor RME (red).
Abdulrazzaq 6
Figure 3 ;( Heijnen, D., Zuijlen, Tosi, & Feringa, 2019).
Heijnen et al., 2019, setup shows a total atom economy of 0.67 using commercially available
starting materials, and the resulting RME (22 percent) is nearly twice as high as that of Knochel,
1997(11 percent). This recent process has advantages as LiBr, NaCl, and HCl are the only waste
sources, the reaction may be performed at a little increased temperature with small amounts of
solvent, thus is entirely an economical process.
The synthesized (Z)-tamoxifen was purified using crystallization, extraction, column
chromatography, and distillation to determine the best isolation method. Separation of the
Abdulrazzaq 7
surplus organolithium reagent and the generated lithium bromide from the product is not
difficult. Purification could be accomplished via acid-base extraction or column chromatography.
Although the residual impurity of dehalogenation of starting material behaves almost identically
to the result, flash chromatography generates a pure form of (E/Z)-tamoxifen combination which
can be separated by the RP-preparative HPLC in water/acetonitrile/TFA depending on
manufacturer’s preference.
Finally, the selectivity of (Z)-tamoxifen is increased by carbolithiation of diphenylacetylene
followed by cross-coupling with the suitable 4-Bromo-dimethylamine-ethyl ether (6) which also
results in high yields of up to 65 percent. The purity of the (E/Z)-tamoxifen mixture is subjected
to flash chromatography. This is the far optimization of the process can go as overdoing it could
affect some production steps like isomerization which would later cause issues and affect
purification of the drug thus creating yet another problem.
Tamoxifen has been the gold standard for the endocrine therapy of all segments of estrogenreceptor-positive breast cancer for more than 25 years, and it is listed as an essential medicine for
the treatment of breast cancer by the World Health Organization. It has been licensed by the
Food and Drug Administration (FDA) for the prevention of breast cancer in both pre-menopausal
and post-menopausal women at high risk. This drug has proved the possibility of a non-toxic
tailored cure for breast cancer which seemed like a dream forty years ago (Jordan, 2003).
Estrogens are hormones that limit the menstrual cycle and are required for reproduction and
other processes in females. The purported benefits of endogenous estrogen on women’s
physiology must, however, be weighed against estrogen’s function in carcinogenesis.
Non-steroidal anti-estrogens were discovered by chance, which is a prime example of scientific
serendipity. The substance ethamoxytriphetol (MER25), in Fig. (5) below, was requested to be
Abdulrazzaq 8
examined in an endocrinology study assessing synthetic estrogens. It was tested in a
cardiovascular study at the Merrell Company in Cincinnati, USA. This was triggered by the
structural similarity between ethamoxytriphetol and estrogen trianisylchlorethylene. The research
proved that ethamoxytriphetol was anti-estrogenic, which has potential in, the treatment of
menstruation diseases, blood lipid regulation, atherosclerosis, behavior modification, and
antitumor agents. Even with the known link between ovarian hormones and breast cancer, most
drugs discovered by Upjohn Company were discontinued as experimental treatments due to
extensive side effects, especially with their unknown potential for toxicity.
Figure (5)
Triparanol is a cholesterol-lowering medicine. Lerner 2013, investigated ethamoxytriphetol, the
first non-steroidal anti-estrogen, and discovered that the medicine was only a weakly active antiestrogen and was also too hazardous. The search for highly active or rather more active antiestrogen continued. Clomiphene is a variety of geometric isomers created by combining an antiestrogenic alkylaminoethoxyside chain with an estrogenic triphenylethylene chain.
The tale of tamoxifen’s discovery and development began with human ties, rather than a preplanned endeavor besides ICI Pharmaceuticals Division, the drug’s manufacturer, established
Abdulrazzaq 9
itself as a key player in oncology following this drug. This company now known as AstraZeneca
was interested in the pharmacology of synthetic compounds of triphenylethylene, and ICI
chemists had created a few non-steroidal estrogens that were employed at high doses to cure
breast cancer. Unfortunately, the market for advanced breast cancer treatment was relatively
small, with just a few thousand individuals responding for up to a year compared to the
contraceptive market.
The goal of the company was to create a non-steroidal anti-estrogen with a lower potential to
elevate circulation desmosterol, which was associated with triparanol’s serious toxicity. Their
research led to the discovery of the Trans isomer of a triphenylethylene in the above figure,
which was later dubbed tamoxifen, as a possible safer medication for clinical use.
Throughout the research, there were doubts as to whether the drug worked on humans as it
worked differently in both rats and mice displaying paradoxical complete estrogen-like activities
in mice but not rats. Fortunately, Walpole was interested in cancer treatment and put “control of
hormone-dependent tumors” in the patent for tamoxifen, which was largely focused on “sexual
cycle management.” Numerous tamoxifen applications were considered at ICI Pharmaceutical
headquarters in Alderly Park in 1972, ranging from ovulation inducement to immunotherapy and
menometrorrhagia, but the development program was on the verge of being terminated. The
prospective applications as an ovulation inducer, for various gynecological diseases, or for
management of severe breast cancer in postmenopausal women did not appear to have the
potential for broad market exploitation or revenue growth to balance clinical research costs.
Despite this, Walpole was able to persuade ICI Pharmaceuticals to commercialize tamoxifen in
the UK as a breast cancer treatment in 1973 and as an ovulation inducer in 1974. (1975).
Abdulrazzaq 10
While it is impossible to properly capture the widespread clinical apathy about the production of
novel endocrine therapy for the management of metastatic disease, opinion leaders’ perspectives
can be recalled by reading their official review articles. Anti-oestrogens’ potential as post-coital
contraceptives was the subject of Emmens’ research. The first significant assessment of antiestrogenic basic clinical usage was done by Lunan and Klopper in 1975. This research focused
on the growing corpus of research on anti-estrogens clinical utility in reproductive
endocrinology, rather than breast cancer. “Relatively little work has been done to translate the
outcomes of animal research to humans,” the study concludes, “but there is now enough evidence
to suggest that antioestrogens have a great potential application to human therapy.” Customizing
anti-estrogens for specific reasons, such as ovulation induction, antifertility, or anticancer, is a
viable technique.”
Whereas tamoxifen was certified for clinical use in the United Kingdom in 1973, significant
work remained to be done to transform an essentially orphan drug with commercial prospects
into a groundbreaking pharmaceutical. This was to be accomplished by employing Ehrlich’s
principles of targeting disease with a laboratory test system. The dimethylbenzanthracene
(DMBA)-induced rat mammary carcinoma model was used to re-invent a medication identified
in a fertility-control study as a groundbreaking therapy for breast cancer.
Tamoxifen wasn’t the only non-steroidal anti-estrogen to be produced for clinical use, but it was
a game-changing drug with widespread use as a breast cancer endocrine therapy. Interestingly,
tamoxifen’s 40-year history paved the way for the development of raloxifene for the treatment
and prevention of osteoporosis, as well as the current testing of raloxifene as a breast-cancer
chemo preventive remedy. It is now proven to lower the risk of breast cancer and is being
compared to tamoxifen in a growing randomized clinical trial called the Study of tamoxifen and
Abdulrazzaq 11
raloxifene. Interestingly, raloxifene was developed as a breast cancer medication in the 1980s but
later shut down due to the drug’s ineffectiveness and cross-resistance to tamoxifen. The
discovery of endometrial cancer linked to tamoxifen and the discovery of non-steroidal anti
estrogens’ bone-preserving or bone-building properties changed that opinion, and raloxifene was
resurrected as a SERM. Based on tamoxifen’s paradoxical pharmacology in diverse tissues and
animals, a new pharmacological class called SERMs has been created. Unfortunately, novel
SERMs or designer estrogens are urgently needed to increase the favorable effects of estrogen
selectivity. Hormone replacement therapy has been shown in prospective studies to reduce
osteoporosis and colon cancer in postmenopausal women, but it also increases the risk of
cardiovascular disease, blood clots, and breast cancer. There is potential for tailored medication
development and the process to refine the anti-estrogen endocrine therapy has led to the
discovery and creation of a new generation of aromatase inhibitors and pure anti-estrogens. Pure
anti-estrogens and aromatase inhibitors are both directed at the same target in breast tumors: the
estrogen receptor. They work hand in hand in hand to kill the estrogen receptor in tissues
throughout the body and prevent estrogen synthesis in postmenopausal women respectively.
These novel targeted anticancer medicines are proving to be successful and appear to be superior
to tamoxifen and if developed further for use there may be more repercussions associated with
Abdulrazzaq 12
the no estrogen approach compared to the balanced SERM method.
Figure (6)
The therapeutic impact of tamoxifen and a better understanding of its pharmacology has
promoted the growth of selective estrogen-receptor modulators (SERMs), third-generation
aromatase inhibitors (anastrozole, letrozole, and exemestane), and a novel pure anti-estrogen.
Most crucially, the SERM principle is already being applied to other members of the steroid
hormone superfamily of receptors, as evidenced by the therapeutic use of raloxifene in
preventing osteoporosis while maintaining breast and endometrial safety.
The implementation of the principle of selective estrogen-receptor modulation to other members
of the superfamily of cell surface receptors and relevant molecules has been prompted by the
therapeutic advance with tamoxifen for the targeted treatment and prevention of breast cancer, as
well as the laboratory data that translated to the clinic. Treatment of inflammation with
glucocorticoids while avoiding negative effects on bone density or designing androgens that are
anabolic while avoiding negative effects on other androgen different tissues are dreams which
can come true come true with research on tamoxifen drug (Jordan, 2003).
Abdulrazzaq 13
The Cre/loxP system, which allows for inducible gene alteration, is a useful tool for studying
gene function in dormant animals. The GFAP-Cre transgenic mice were designed to accomplish
gene recombination in astrocytes, which are the most abundant cells in the central nervous
system and play a key role in brain function and pathology. However, because of GFAP
promoter is strong in embryonic radial glia, as it has a high neurogenic potential, these mice also
showed neuronal recombination. Transgenic animals with CreERT2, a fusion protein of the DNA
recombinase Cre and a mutant ligand-binding domain of the estrogen receptor, expressed under
the control of the human GFAP promoter were used, to allow temporal control of gene deletions
in astrocytes only. Consecutive intraperitoneal doses of tamoxifen triggered genomic
recombination selectively in astrocytes of practically all brain areas in offspring derived from
interbreeding of GFAP-CreERT2-transgenic mice with various Cre-sensitive led animals.
Almost all cells of Bergmann glia, which represent the cerebellum’s primary astroglial cell type,
displayed effective gene recombination. Adult mice given tamoxifen while receiving cortical
stab wound lesions showed significant recombination in reactive glia proximal to the injury site.
The functional study of loxP-modified genes in the astroglia of the postnatal and adult brain will
be possible with these transgenic GFAP-CreERT2 mice. (Hirrlinger et al., 2006).
Abdulrazzaq 14
Figure (7): Mouse Breeding with Cre/lox. Mice containing a gene function framed by loxP sites
are bred with mice expressing the Cre protein in a progenitor cell. Once the mice are bred, the
Cre-carrying cells will cause the target gene to be lost in those cells. (Alfredpechisker, 2004).
The development of long-chain lipid and oil-based nanostructured lipid carrier systems is a
unique strategy for boosting tamoxifen uptake via the Intestinal Lymphatic System (Tmx-NLC).
The goal was to improve tamoxifen’s systemic bioavailability, avoid systemic and hepatotoxicity,
and boost anticancer effectiveness. Supporting proof of concept in cell culture tests and an in
vivo pharmacokinetics and bio distribution analysis, the current research focuses on antitumor
efficacy and treatment-related toxicity in a murine mammary tumor mouse model. When
compared to 3 mg/kg tamoxifen suspension and Mamofen®, 1.5 and 3 mg/kg Tmx-NLC showed
higher tumor suppression and 100 percent survival (Khandelwal Pharmaceuticals, Mumbai,
India). Following a recent month of Tmx-NLC treatment, the systemic toxicity profile improved
and there was no evidence of hepatotoxicity. As a result, the proposed Tmx-NLC could be a
Abdulrazzaq 15
viable delivery approach for conferring greater therapeutic efficacy as well as the ability to solve
the drug’s biological and toxicity-related concerns. Following the figure (2). (Shete et al., 2014).
The anti-estrogen medication tamoxifen has been widely utilized to treat breast tumors that
express estrogen receptors (ER). Unfortunately, endocrine treatment resistance is seen in up to
50% of all ER-positive malignancies. Recent research has indicated that the ER captivator
Mediator Subunit 1 (MED1), through crosstalk with HER2, plays a significant role in tamoxifen
resistance. Using a HER2 RNA aptamer to inhibit MED1 expression, a three-way junction (3WJ) pRNA–HER2apt–siMED1 nanoparticle was created to target HER2-overexpressing human
breast cancer. It was discovered that these ultra-compact RNA nanoparticles are extremely stable
in the presence of RNase A, serum, and 8 M urea. These nanoparticles adhered to HER2overexpressing breast cancer cells selectively, effectively depleted MED1 expression, and
drastically reduced ER-mediated gene transcription, whereas point mutations in the HER2 RNA
aptamer on these nanoparticles eliminated these effects. The RNA nanoparticles not only
inhibited HER2-overexpressing breast cancer cells proliferation, metastasis, and mammosphere
Abdulrazzaq 16
formation but also made them more susceptible to tamoxifen treatment. After systemic injection,
these bio-safe nanoparticles efficiently targeted and penetrated HER2-overexpressing tumors in
orthotopic xenograft mice models. When paired with tamoxifen treatment in vivo, these
nanoparticles significantly reduced the stem cell content of breast cancers, in addition to
drastically inhibiting tumor growth and metastasis. Overall, it was possible to create
multifunctional RNA nanoparticles that targeted HER2-overexpressing human breast cancer,
suppressed MED1, and overcame tamoxifen resistance. As the figure (9) below shows
Figure 9.
Abdulrazzaq 17
Figure (10): Nanoparticles of pRNA–HER2apt–siMED1 were created and characterized. (A) The
structure of pRNA–HER2apt–siMED1 (p-HER2-siMED1). (B) The p1 and p2 strands of pRNA–
HEonR2apt–siMED1 were transcribed and separated in an 8 percent denatured PAGE gel
utilizing an in vitro RNA transcription system. (C) Nanoparticles of pRNA–HER2apt–siMED1
were made by annealing equal quantities of strands p1 and p2 and electrophoresis on an 8
percent native PAGE gel. (D) DLS assay of pRNA–HER2apt–siMED1 nanoparticle
hydrodynamic size. (E) TGGE assay was used to measure the Tm value of the pRNA–HER2apt–
siMED1 nanoparticle. (F) Images of pRNA–HER2apt–siMED1 nanoparticles obtained using
atomic force microscopy (AFM). (G) After RNase A, 10 percent FBS-supplemented DMEM
Abdulrazzaq 18
media, and 8 M urea treatments for the given duration at 37 °C, the stability of control
unmodified and 2′-F-modified pRNA nanoparticles was assessed by 8 percent native PAGE gel
electrophoresis. (Zhang et al., 2016).
Figure (11): In vitro and in vivo, pRNA–HER2apt–siMED1 nanoparticles specifically targeted
BT474 cells. (A) Confocal microscopy studies of AF647-labeled control and pRNA–HER2apt–
siMED1 nanoparticle internalization by BT474 cells. The scale bar is 10 meters. (B) Cellular
Abdulrazzaq 19
uptake of AF647-labeled control and pRNA–HER2apt–siMED1 nanoparticles by BT474 cells as
measured by flow cytometry. (C) 24 h following IV administration of specified AF647-labeled
pRNA nanoparticles (10 mg/kg), IVIS Lumina live imaging of BT474 orthotropic xenograft
mice. (D) The above mice’s major organs and tumors were removed and examined for AF647
fluorescence. (E) Confocal microscopy was used to look for AF647-labeled pRNA nanoparticles
(red) in frozen tumor sections. Anti-CD31 primary antibody and Alexa488-conjugated secondary
antibody were used to stain the blood vessels (green). DAPI was used to stain the nuclei (blue).
The scale bar is 50 meters. (F) Image-pro Plus software was used to measure the fluorescence
intensity of AF647-labeled pRNA nanoparticles (red) in frozen tumor sections. (Zhang et al.,
2016).
Abdulrazzaq 20
Figure (12): In vitro, pRNA–HER2apt–siMED1 nanoparticles repressed MED1 expression and
decreased HER2-positive breast cancer cells’ growth and spreading capacities. (A) For 48 hours,
BT474 cells were treated with 10 g/mL control and pRNA–HER2apt–siMED1 nanoparticles, and
the quantity of MED1 mRNA was measured using real-time PCR. (B) BT474 cells were treated
directly with (as indicated by –) or lipofectamine 2000 transfected with specified pRNAs.
Western blotting was used to evaluate MED1 protein levels 48 hours after therapy. (C–E) BT474
cells were treated with 10 g/mL pRNA nanoparticles for 48 hours and cell viability was
Abdulrazzaq 21
determined using the MTT test (C). Cells were treated as described above and planted in
Transwell experiments for migration (D) and invasion (E). The scale bar is 50 meters. (F–H)
Real-time PCR was used to evaluate the mRNA levels of ER target genes TFF-1 (F), c-Myc (G),
and cyclin D1 (H) in BT474 cells after 48 hours of pRNA treatment. (Zhang et al., 2016).
Figure (13): Western blotting was used to evaluate MED1 protein levels 48 hours after therapy.
(C–E) BT474 cells were treated with 10 g/mL pRNA nanoparticles for 48 hours and cell viability
was determined using the MTT test (C). Cells were treated as described above and planted in
Trans good experiments for migration (D) and invasion (E). The scale bar is 50 meters. (F–H)
Real-time PCR was used to evaluate the mRNA levels of ER target genes TFF-1 (F), c-Myc (G),
and cyclin D1 (H) in BT474 cells after 48 hours of pRNA treatment. (Zhang et al., 2016).
Abdulrazzaq 22
Figure (14): In vivo, pRNA–HER2apt–siMED1 nanoparticles suppressed the development of
HER2-overexpressing breast tumors. (A) BT474 orthotopic xenograft mouse models were given
pRNA–HER2apt–siScram or pRNA–HER2apt–siMED1 (4 mg/kg) once a week, in addition to
vehicle or tamoxifen (TAM, 0.5 mg/mice/day) five times a week. Every three days, the tumor
size was measured. (B) Mice were injected i.p. with d-luciferin after 3 weeks, and representative
in vivo images of BT474 tumors was captured using the IVIS Lumina imaging system. (C, and
D) The average weight of tumors excised at the end of treatment (C), as well as sample tumor
photographs (D). (E-G) IHC labeling (E and F) and immunoblotting were used to look at MED1
expression in BT474 tumors (G). (Both H and I) IHC staining (H) was used to examine Ki-67
Abdulrazzaq 23
expression in tumor tissues, and the percentage of Ki-67 positive cells was calculated (I). The
scale bar is 100 meters. (Zhang, et al., 2016).
Figure (15): In vivo, the combination of pRNA–HER2apt–siMED1 and tamoxifen significantly
reduced breast cancer lung metastasis, stem cell production, and related gene expression. (A and
B) Metastasis foci in entire lung tissues were counted after they were fixed, embedded, and
sectioned for H&E staining (A) (B). The metastatic foci were marked by a red arrow. The scale
bar is 100 meters. (C and D) Tumor cells were labeled for CD44 and CD24 and examined for
CD44+CD24/low stem cell population using flow cytometry after digestion with trypsin and 0.1
percent collagenase. (E–H) Total RNA was isolated from tumor tissues using TRIZOL reagent,
Abdulrazzaq 24
and real-time PCR was used to evaluate the expression of TFF-1 (E), c-Myc (F), and cyclin D1
(G), and MMP-9 (H). (Zhang et al., 2016).
Considering all the facts, Estrogens are hormones that regulate the reproductive period and are
necessary for successful reproduction. There is a known link between ovarian hormones and
breast cancer growth. Anti-estrogen treatments have been used as a treatment for breast cancer
with one such drug being tamoxifen. There have been many manufacturing processes for this
drug, but the best so far has been the two-stage process which involves direct and cross-coupling
of reagents using a nanoparticle palladium metal catalyst. This is an economical process that
produces a highly selective type of tamoxifen with low toxicity and specifically no
hepatotoxicity. Most anticancer drugs fail to pass the toxicity and side effect test but not
tamoxifen as it has been approved by the World Health Organization and licensed by the FDA as
a safe cancer treatment. In breast tumors, aromatase inhibitors and pure anti-estrogens both target
the same target: the estrogen receptor. Aromatase inhibitors block estrogen synthesis in
postmenopausal women, but pure anti-estrogens eliminate the estrogen transporter in tissues
throughout the body. RNA Nanoparticles were shown to weaken breast cancer cells making them
susceptible to the tamoxifen medication. This reduces resistance to the cancer drug in breast
cancer patients.
Abdulrazzaq 25
References
1.
Alfredpechisker, TARGETING YOUR DNA WITH THE CRE/LOX SYSTEM, August
2004, https://www.scq.ubc.ca/targeting-your-dna-with-the-crelox-system/
2. Biochem J., (2009), New anti-cancer role for PDK1 inhibitors,
https://portlandpress.com/biochemj/article-abstract/417/1/e5/45199/New-anti-cancer-role-forPDK1-inhibitors
3. Heijnen, D., Zuijlen, Tosi, & Feringa, An atom efficient synthesis of tamoxifen, Org. Biomol.
Chem., 2019, 17, 2315-2320, https://pubs.rsc.org/en/content/articlehtml/2019/ob/c8ob02977f
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