Advanced Cancer Treatment Research and Education Center … · 24.Gaurav Wagle 25.Jyoti Sharma...
Transcript of Advanced Cancer Treatment Research and Education Center … · 24.Gaurav Wagle 25.Jyoti Sharma...
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Advanced Cancer Treatment Research and Education Center (ACTREC)
visit report
The Students of M Pharmacy of Oriental College of Pharmacy visited ACTREC
i.e. Advanced Centre for Treatment Research and Education in Cancer which is
located at Kharghar. ACTREC is a state-of-the-art cancer research institute which
is basically a sister organisation of the Asia‟s largest cancer treatment centre, The
Tata Memorial Hospital. The visit was scheduled for M pharmacy students only on
5th
of March , 2015.
Following students and staff attended the visit:
STUDENTS
1. Misbah Badewale
2. Deepali Jadhav
3. Sarika Kadam
4. Azhar Kamal Khan
5. Vedang Kinjawadekar
6. Mohammed Shadab M.
7. Vanita Panda
8. Lydia Jeeboi
9. Varsha Andhale
10. Priyanka Chauhan
11. Reha Chodankar
12. Seema Desai
13. Anuja Dhas
14. Ankita Dhumal
15. Jagruti Karanjavkar
16. Swapnil Lembhe
17. Avanti Mhatre
18. Priyanka Patil
19. Kalim Khan
20. Akshay Khot
21. Prajakta Pawar
22. Padmaja Rao
23. Arifa Sangle
24. Gaurav Wagle
25. Jyoti Sharma
26. Amogh Lotankar
STAFF: Dr. Mrs. Vanita Kanase, Mr. Imtiyaz Ansari, Mr. Sayyed Mateen,
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The institute is located on the foothills of the Sahyadri Mountain range which
makes the whole campus serene and apt for research. The visit started by a brief
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presentation given by Dr.Aparna .N. Bagwe, Scientific Officer „F‟ ,Officer in
charge, SCOPE Cell ACTREC, Tata Memorial Centre.
She briefly explained everything about the institute i.e. The history of the institute,
the hierarchy in the organisation, the labs, the equipment, the scientists involved
and their contribution. She also highlighted the various career options and training
programs for the students of pharmacy. Regarding the organisation of the institute
ACTREC is a part of Tata Memorial Centre. It is further branched into Cancer
research Institute, which conducts basic research and the Clinical Research
department which handle the clinical research. ACTREC is a huge institute so
visiting each and every facility that they have was not possible as there was a time
constrain. So Four main areas were chosen and we were allowed to visit those four
areas namely Anti cancer drug screening , clinical pharmacology dept., Mass
spectrometry and UPLCs and X ray crystallography. The Whole group was
divided into three small groups headed by one of the accompanying faculty
members and each group visited each of the mentioned facilities.
The first unit was the Anti-Cancer Drug Screening Facility(ACDSF)
Scientific officer: Kode Jyoti, in-charge, Technical officer: Kasinathan Nirmal
Kumar
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The mandate of ACDSF is to provide support in the efforts of drug development in
India, in terms of in vitro and in vivo anti-cancer drug screening for academicians
as well as private companies. ACDSF has over 45 human tumor cell lines, 10
murine tumor models and 28 xenograft models for carrying out drug screening. In
vitro screening is carried out using SRB assay as per the protocols approved and
recommended by NCI, USA; the complete SRB assay set up has been developed
and standardized in house. In vivo testing involves dose finding studies and
efficacy testing of experimental drugs in murine and human tumor xenograft
models. The facility is fully equipped for carrying out the in vitro and in vivo
testing. ACDSF has the expertise and established infrastructure of biosafety
cabinets, laminar air flow systems, automated liquid handling systems, ELISA
plate readers, mobile anesthesia machine. A database of cell lines in terms of
quality control parameters like morphology, Mycoplasma testing, doubling time
and karyotyping has been established.
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The next unit was the Clinical pharmacology lab where resource intensive phase
I clinical trials and bioequivalence studies initiated by Indian or multinational
pharmaceutical industry as well as academic investigators is conducted. The unit is
supervised by Dr. Vikram Gota, a clinical pharmacologist with training and
experience in conducting early phase clinical trials, drug development and
pharmacokinetic studies. A team of Clinical Pharmacologists, Medical
Oncologists, Pharmaceutical scientists, Clinical Trialists and Bio-Statisticians are
responsible for the design and/or conduct of early phase clinical studies. The unit is
manned by specialist registrars and research nurses round-the-clock with internal
and external audits as per regulatory requirements. Supporting services include an
NABL accredited composite lab for routine laboratory investigations, a clinical
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pharmacology lab with facilities for sample processing and storage, ACTREC has
an IRB comprised of eminent clinicians and scientists constituted as per ICMR
norms, with an average time of 6 weeks from submission to approval.
This unit also deals with Therapeutic Drug Monitoring(TDM). Therapeutic drug
monitoring (TDM) is a branch of clinical pharmacology that specializes in the
measurement of medication concentrations in blood. Its main focus is on drugs
with a narrow therapeutic range, i.e. drugs that can easily be under- or overdosed
like the anti cancer drugs. It is aimed at improving patient care by individually
adjusting the dose of drugs for which clinical experience or clinical trials have
shown it improved outcome in the general or special populations.
The other main focus of the clinical pharmacology lab is the Bioavailability and
bioequivalence studies (BA/BE studies). Bioavailability and/or Bioequivalence
(BA/BE) studies play an important role during the process of drug development
and it applies to both new drugs as well as to their generic counterparts. BA/BE
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studies are also vital for the post approval process due to changes done in
manufacturing of drugs. Studies on Bioavailability (BA) and Bioequivalence (BE)
play a key role in providing information to ensure the availability of safe and
effective medicine to the patients. BA and BE gained much interest during the last
few decades after it became known that marketed products having the same
amounts of the drug may exhibit marked differences in their therapeutic responses.
Following were the equipments and processes in bioanalytical section which were
demonstrated to students:
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1. Mass spectrophotometer:
Cancer is a multigenic disease, and the study of molecular alterations which lead
to tumorigenesis as well as those that are the outcome of tumor formation is
receiving considerable attention. The development of various global profiling
technologies has led to a major spurt in information about such molecular
alterations, in the „omics‟ era.
A technological advance which has revolutionized proteomics is biological mass
spectrometry. Today, it is possible not only to identify proteins which are
differentially expressed in transformed and non‐transformed tissues, but also to
home in on differences in their post‐translational modification.
ACTREC houses a state‐of‐the‐art Mass Spectrometry facility, which is used by
several research groups at the Centre to answer diverse queries in Cancer
Biology. The principle behind the MALDI‐TOF/TOF instrument which is used to
identify proteins separated on 2D gels.
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The use of mass spectrophotometer was demonstrated for cancer research. 2
instruments of mass ie QTOF and MALDI were shown. The use of these two in
cancer detection and treatment was overviewed by the competent staff of
ACTREC. Use of LC-MS in screening of the samples of cancer cells obtained
from the patients was demonstrated effectively. It thus provided the idea of use and
basic principles of using mass spectrophotometer in cancer research. It was 1st time
students got to see the MS as it costs around 25 crores and thus not so easily
available. The MS demonstration was useful as part of study in practical aspects of
how the mass to charge ratio affects the samples and how it can be used in cancer.
The use of High Performance Liquid Chromatography along with use of higher
pressure and better instrument UPLC was demonstrated by ACTREC staff.
Sampling techniques along with details was emphasized upon. Students were
shown the automated instrument along with its internal parts and working.
Sequential procedure of operating UPLC, components of it, analytical method
development, and use of appropriate solvent systems for samples were shown.
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Students had good interaction with the staff about use of UPLC and gained
practical knowledge and skills to handle the instrument and obtain appropriate
results. Determination of cancer cells using high throughput screening using this
bioanalytical method was explained to the students.
2. X-Ray Crystallography:
X-ray crystallography can reveal the detailed three-dimensional structures of
thousands of proteins. The three components in an X-ray crystallographic analysis
are a protein crystal, a source of x-rays, and a detector.
X-ray crystallography is used to investigate molecular structures through the
growth of solid crystals of the molecules they study. Crystallographers aim high-
powered X-rays at a tiny crystal containing trillions of identical molecules. The
crystal scatters the X-rays onto an electronic detector. The electronic detector is the
same type used to capture images in a digital camera. After each blast of X-rays,
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lasting from a few seconds to several hours, the researchers precisely rotate the
crystal by entering its desired orientation into the computer that controls the X-ray
apparatus. This enables the scientists to capture in three dimensions how the crystal
scatters, or diffracts, X-rays. The intensity of each diffracted ray is fed into a
computer, which uses a mathematical equation to calculate the position of every
atom in the crystallized molecule. The result is a three-dimensional digital image
of the molecule.
Crystallographers measure the distances between atoms in angstroms. The perfect
“rulers” to measure angstrom distances are X-rays. The X-rays used by
crystallographers are approximately 0.5 to 1.5 angstroms long, which are just the
right size to measure the distance between atoms in a molecule. That is why X-rays
are used.
Some of the advantages of X-ray crystallography are that the technique itself can
obtain an atomic resolution structure even if the atomic structure is in solution.
This is because the structure in crystal form is the same if it were in solution.
Another advantageous aspect is that atomic structure contains a huge amount of
data pertaining to the crystallized pure protein.
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The information one could receive from the structure of the protein can provide
more information then finding its niche in the cellular environment.
A huge instrument setup of X-Ray crystallography was demonstrated to students
by experienced staff. The study involved proteins and its internal structure along
with its representation in a crystallogram was shown. Identification of specific
proteins which are involved in cancer cells and which should be targeted for its
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effective treatment was demonstrated to the students. Detailed information about
parts of X-Ray crystallogram and need for its study was emphasized. Use of
softwares which can help predict the structure of proteins using X-Ray
crystallography was taught to students. It was a great and interactive session filled
with knowledge about analytical technique.
The first step in structure determination by X-ray crystallography is the
crystallization of the protein. The source of the X-rays is often a synchrotron and
in this case the typical size for a crystal for data collection may be 0.3 ¥ 0.3 ¥ 0.1
mm. The crystals are bombarded with X-rays which are scattered from the planes
of the crystal lattice and are captured as a diffraction pattern on a detector such as
film or an electronic device. From this pattern, and with the use of reference—or
phase—information from labeled atoms in the crystal, electron density maps
(shown here with the corresponding peptide superimposed) are computed for
different parts of the crystal. A model of the protein is constructed from the
electron density maps and the diffraction pattern for the modeled protein is
calculated and compared with the actual diffraction pattern. The model is then
adjusted—or refined—to reduce the difference between its calculated diffraction
pattern and the pattern obtained from the crystal, until the correspondence
between model and reality is as good as possible. The quality of the structure
determination is measured as the percentage difference between the calculated
and the actual pattern.
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The above instruments and bioanalytical techniques were useful for students of
QA as per their analytical syllabus.