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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.