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Jellyfish inspires cancer diagnosis
One of the biggest challenges in cancer lie in its early diagnosis. Owing to its asymptomatic
nature, most cancers remain undiagnosed until they undergo metastasis, that is, gain the ability
to bud off from their primary site and spread through the circulatory system. Scientists have
come up with various tools that enable the early diagnosis of cancer over the past decade but
there is a continual need to improve their efficiency and sensitivity. Cancer is a heterogeneous
disease and therefore it is imperative to understand the nature of the cancer cells, in order to
formulate a suitable route of treatment.
The most commonly used procedure to confirm if a lesion is cancerous is a tissue biopsy, an
invasive procedure that cannot be repeated and fails to detect metastasis at distant sites. Then
came liquid biopsy, which focusses on the detection of circulating tumour cells (CTCs), which
are metastatic cancer cells that have been shed from the primary tumour.
The conventional method of liquid biopsy is complex, multistep and inefficient, such as
®
immunomagnetic enrichment or flow cytometric cell sorting. CELLSEARCH is one such
method approved by the FDA that uses immunomagnetic enrichment, and is currently used for
the detection of breast, colorectal and prostate cancer. More recent technology includes
microfluidic devices that uses antibodies or nucleic acid aptamers for capture which is great if
not for these drawbacks.
o CTCs make up a very tiny fraction of cells in our bloodstream, and an effective
diagnostic will have to process large volumes of blood.
o Though these devices offer greater simplicity, sensitivity and throughput, these
monovalent adhesion ligands can extend only a few nanometers into the solution. The
prototypes still feature very narrow microchannels to ensure that the CTCs pass within
reach of their antibodies along the perimeter. They fail to capture large-sized entities
like cells under high shear stress.
o The cell separation devices generally fail to release captured cells gently, and this could
upset the subsequent molecular analyses that screen for effective chemotherapeutic
drugs.
The race to find a single system to combat all these disadvantages saw biomedical engineer
Jeff Karp turn to nature for a solution. They were looking at creatures that capture things
effectively at a distance. “Why not jellyfish?!” said one of his students. These sea animals have
long sticky, tentacles to grab prey and other food particles from water.
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A common feature of these tentacles is that they are long, extend into the flow, and contain
repeating units of adhesive moieties (e.g., mucus), which maximizes the contact with flowing
targets and therefore the capture efficiency.
And voila! A microfluidic chip that can isolate flowing entities which means cancer cells in
peripheral blood! The chip contains 800-micron wide microchannels, lined with long, tentacle-
like strands of DNA molecules containing multiple target-binding aptamers [Synthetic
stretches of oligonucleotides or polypeptides that can bind specifically to a particular protein].
This feature increases avidity without compromising the capture efficiency.
A microfluidic chip with channels lined with DNA strands containing multiple target-binding aptamers
resembling the tentacles on a jellyfish.
Dr.Karp’s device can process 10 times more blood than the existing chips in a given amount
of time, and is successful in trapping 50% of leukemia cells! DNA strands extending into the
3D space can increase the accessibility and frequency of interactions to permit cell capture
under high flow rates. Finally, the DNA strands can be cleaved by restriction enzymes, which
permits the captured cells to be easily released for molecular analysis.
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A closer look into the cancer-cell capture device. The box that is zoomed-in illustrates a captured cell
bound by several long DNA molecules via multiple aptamer domains (red color).
It is estimated that a microchip the size of a standard microscopic slide could capture hundreds
of thousands of tumour cells. These promising results have encouraged the scientists to work
on prototypes that can be used to capture any CTC of interest.
Karp predicts that this device could be useful in prediction of cancer relapses and for screening
drugs for personalized medicine. This approach, once developed, will have broad applications
not only in the detection, but also in isolation, enrichment and sorting of rare cell types (such
as cancer cells or pathogens) for applications in diagnosis.
Nature is the epitome of biomedical solutions. According to Donald Ingber, founding director
of the Wyss Institute for Biologically Inspired Engineering in Boston, “Nature has used the
power of evolution by natural selection to develop the most efficient ways to solve all kinds of
problems.”
We just need to look in the right direction!
Presented by
Rithika Suresh
Associate Editor
Click on the hyperlinks to jump into our knowledge fountains
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05
World Cancer Day celebration in Poseidon Town
Diego: Hey! Did you know that our Stem Cell and Omics editions were a huge hit with the
people on Mainland!?
Godin: That's great to know. We must definitely credit Odin for taking ‘em to them!
Diego flipping through a newspaper
Diego: Did you know, cancer is the #1 killer on mainland and coincidentally February 4th is
the World Cancer Day.
Godin: But why cancer out of the blue? Is there something that we can do?
Diego: (still reading the newspaper) Fun fact, sharks never get cancer since they only have
cartilages and no bones.
(Looking at a puzzled Godin) And there is in fact something we can do; this year's theme is ‘I
can, we can’. It acknowledges the capacity to address the cancer menace and we can overcome
these barriers by improving early diagnosis, treatment and palliative care.
Odin drops by them
Odin: Hey guys! What's up?
Godin: We were thinking of taking up Cancer for our next coverage and have a small
competition maybe, where the kids from PHSS could present a skit in light of this year's World
Cancer Day theme of, 'I can, we can'.
Diego: Each of them would get 3 minutes to present their skit, the idea is to show the symptoms
and prevention for different types of cancer.
Odin: That's really a good idea you guys, why don't we talk to Beulah regarding this idea and
draw up dates for the competition. Or better, we have our week long Annual Poseidon town
fair in the upcoming week, why don't we have it then?
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“Let’s goooo!” squeal Diego and Godin in unison.
They all meet with Beulah the Blue Whale
Beulah: (cheers excitedly) We will definitely have this. Let me call Ms. Cuppy who is the
senior member of the turtle bale and the proud headmistress of the school and inform her about
the competition.
Ms.Cuppy: Yes Madam Mayor! Please tell me.
Beulah fills her in about the idea of having a Cancer Day awareness programme. Ms.Cuppy
gets visibly very excited about the idea and gives a nod!
Beulah: So boys get ready with the preparation, for the competition is officially on!
Over the next few days the boys engage themselves in the preparatory work for the
competition.
The day of the competition draws nearby and every student is engaged in one way or the other.
The eels help make the placards, Sharks are the bouncers for the day, Starfish are in the
refreshments committee. The school of fish is in palpable excitement and putting on their
costumes.
The parents of the school kids and other common folk fill into the amphitheatre and Beulah is
the chief guest for the night.
After the presentation, Odin takes over the podium.
Odin: A very big applause to all the participants and their infectious enthusiasm this evening!
Another big round of applause for Diego and Godin for brainstorming and coming up with this
idea. Now I call upon Mayor Beulah to give away the prizes!
Beulah: Hello all! It gives me great honour to be here today and give away the prizes.
Everybody here is a winner today, for you have spread the awareness regarding the dreadful
malady and saved many lives in retrospection.
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The third prize goes to asgardians for their portrayal of genitalia cancer. Being a sensitive issue
which is brushed under the carpet, this group of Seahorses have subtly put across the issue.
The second prize is a tie between two teams. ‘Wingx Club’, an all girls shark team and
‘Animo’, a mixed group of crabs and clams for their skits on Gastric cancer and Melanoma
respectively.
Before I announce the First prize, I must applaud the mentor of this team who has not only put
across the message of cancer prevention but also feminism. The winner of the first prize is
‘The Ocean troopers’, an all male group of Dolphins who beautifully presented a skit on breast
cancer awareness. They never flinched for a second neither were they awkward talking about
the same. Very good job boys!
Dressed in pinks, the Dolphins couldn't have been much happier. Freddie, the leader of the
group spoke up
Freddie: From the very beginning we wanted to raise awareness regarding this issue, since it
is really common and also a large number of ladies suffer from this. They are our caretakers
as mothers, sisters, teachers, nurses and friends and it is time we lend our hand and support
their cause.
The ocean troopers received their shields with a roaring applause from the crowd and they
called it a day!
Conceived by
Rakshana R
Senior Editor
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Benign Beliefs
Myth: Herbal products can cure cancer. person to person is via organ transplantation
if the donor has a history of cancer. But in
Fact: Studies show that herbal products most cases donors with cancer history are
have shown to be ineffective in treating rarely considered for transplantation. While
cancer, however alternative and cancer by itself is not contagious, there are
complementary therapies using some herbs, several bacteria and virus that cause cancer in
have shown to help patients cope with side humans and they are capable of spreading
effects of cancer treatment. Perhaps it is from one person to another.
advised to consult a doctor in advance as Myth: Artificial sweeteners can cause
certain herbs can be harmful and worse, can cancer.
interfere chemotherapy and radiation therapy
treatments. Fact: No, artificial sweeteners are not
carcinogenic. The controversy surrounding
Myth: Cancer surgery and tumor biopsy artificial sweeteners started when European
cause cancer to spread to other parts of the scientists found increased incidence of
body.
bladder cancer in laboratory rats that were
Fact: Surgery and biopsy are done with administered saccharin. However, further
extreme care and precaution using studies in humans have ruled out the risk of
standardized procedures and so spreading of cancer due to the consumption of artificial
cancer during tumor removal is completely sweeteners. The FDA and EU have approved
prevented. Performing a tissue biopsy is their use stating they do not pose a cancer risk
highly essential in the diagnosis of cancer and when consumed in recommended amounts,
surgery is known to completely cure early- which means you can cut down on your
stage cancers. As the common man knows it, calories and not worry about ending up with
no surgical equipment is reused in hospitals cancer.
today. Moreover, removal of tumors from Myth: Hair never grows back after a
different areas are done using different chemotherapy.
surgical tools for each new area. Also studies
show that spreading of cancer due to surgery Fact: Firstly, not all chemo drugs cause hair
is extremely low. loss but a majority of them do. The fact is
99% of the patients undergoing
Myth: Cancer is contagious.
chemotherapy will have their hair grown
Fact: Cancer is not an infectious or back in 3-6 months after complete treatment
communicable disease and so it cannot be depending on the dosage and frequency of the
transmitted from person to person. The only drug(s) administered. Research suggests the
known way in which a cancer spreads from chemo drugs disrupt the vascular network
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associated with hair-follicles but not the hair- But be vigilant! Never ignore a persistent
follicle stem cells which explains the hair lump or a change in the breast tissue. Only
regrowth post chemotherapy. But in certain your physician can determine if it is benign
cases patients have had a permanent effect or malignant.
leading to no hair growth mainly due to the
high-dose or intravenous chemo or Myth: Use of Antiperspirants and
combination regimens especially involving Deodorants can cause breast cancer.
doxorubicin, docetaxel, paclitaxel or
etoposide. Fact: The principle component of
antiperspirants and deodorants is aluminium
Myth: A lump in the breast is always breast salts. Aluminium is a metalloestrogen i.e. it
cancer. is capable of interfering with oestrogen
action in the body and increased oestrogen
Fact: A lump is a localized swelling of the
breast tissue and there are a number of causes levels is associated with the risk of breast
cancer. However, research states that there is
as to why they develop. And cancer is just no direct association between the use of
one of them. For example, a breast cyst which antiperspirants/deodorants and the risk of
is a benign, non-cancerous, fluid-filled sac breast cancer.
also appears as a lump. About 80% of the
biopsied breast lumps turn out to be non-
cancerous.
Busted by
Priyadharshini R
Senior Editor
Click on the hyperlinks to jump into our knowledge fountains
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The moment any faculty of our department hears the word cancer
biology, the first name that would pop up in their minds is Sakthi Lalitha
Sri. It has been 10 years since Sakthi joined Rec (Batch2010-14), and
she is still fondly remembered by the faculty as the student who never
fails to wish every teacher on September 5th, every year. Sakthi was keen
on doing Biology from a very young age, and her love for the subject has
only grown from then. Having completed her bachelor’s degree at REC,
she went on to do her Master’s in Life Science Informatics at the
University of Bonn, during which time she found herself working as a
research assistant at Fraunhofer Institute for Algorithms and Scientific
Computing, Bonn. Then, she worked as a JRF at Cancer Institute,
Chennai for 10 months. A certified Programmer in C, C++ with a
certification on Data structures, the sky is the limit when it comes to
Sakthi. A queen of all trades, we could not find a better person to give
us this interview. Read on as Sakthi goes candid about her line of work,
her hobbies and her message for people who aim for a career in Cancer
Research!
While selecting you as the candidate for lot of fun. I have spent most of my time after
this issue’s alumnus interview, we heard class hours in the department staff room with
tonnes of good words about you from our the faculty. If I do get a chance to relive those
department faculty. It has been impossible moments, I will definitely use it in any way
to hear a single negative comment. It is a possible.
feat every student wishes to accomplish. Yourself and cancer biology: Fate or
Can you relive your department days?
Design?
Yes, definitely. Those were my best and most To involve myself in the field of cancer has
memorable days. To me, they were not just the always been my passion and dream. We all
faculty. They were good teachers, guides, know cancer is one of the deadliest diseases in
well-wishers, philosophers and most the world, and ever since I came across and
importantly, best friends. We used to share a started to study about cancer, I had always
lot of things, not only regarding subjects but been wondering about it and was curious to
also our personal lives, made jokes and had a
know what really causes cancer and how it
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alters the genetics in a person. I felt it was than just a theory paper we definitely require
necessary to understand these concepts in a practical exposure to the subject atleast for
detail to be able to help the society and one semester so as to understand the theory
contribute to the healthcare department. which we study. Especially when we want to
pursue higher studies in Cancer biology either
If you weren’t in the field of cancer biology, in India or abroad, we must at least know to
in an alternate universe, what would you be perform and handle the basic techniques like
doing? Would you even be in
biotechnology? cell seeding, passaging, maintaining cell lines
and simple assays like MTT of both normal
If not cancer biology, I would have been a and cancer cells. Personally, I had the
bioinformatician or chemoinformatician as I experience of spending 3 months to get myself
have always been fascinated by the idea of trained in these wet lab techniques when I
using computer technology to solve scientific joined as Research Assistant at Cancer
problems. And I definitely would have Institute, Adyar. So, it would be really helpful
remained in the field of Biotechnology, as it if we learn these techniques earlier as we may
was my dream and passion since 9th grade to not get the chance or time to be trained
pursue a career in this field. I had always everywhere we go.
wanted to finish my bachelors and masters
with specialization, move on to research, Most students taking up biotechnology do
so with dreams of going on the cancer
finish my doctorate in a few years and at last biology path. How much is already known
enter into the beautiful and soulful field of in cancer biology, how much is remaining
teaching. To be a teacher has been my long- to be discovered and from what perspective
term goal since childhood.
will we study cancer?
For a student planning to pursue Cancer From my point of view, I would say that what
biology during higher studies, what are the we learn and what we know is very little,
theory papers they should be proficient in probably just the basics of cancer biology
(based on AU curriculum)?
which might give us an idea of the field. But
The existing cancer biology theory paper in order to work in the field of cancer biology
(based on AU curriculum) is good enough to we need to get ourselves into deeper insights
learn the basics but I believe that instead of an of cancer biology as every type of cancer is
elective, it should be made a mandatory as very different and deals with different
everyone needs to know the basics of cancer metabolic pathways. We should explore it
biology, even if they choose to be in a with a broad perspective of mind as there is no
different field. Additionally, I think that more ending to the subject, especially in the area of
research.
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You have been extensively working in the cases of cancer are linked to genetics. Some of
areas of cervical and oral cancer. Can you them are due to lifestyle, food habits and
give us an idea about your project? environment. Such cases can be avoided by
being cautious and taking appropriate care.
With respect to oral cancer, I was helping a And also, those affected by cancer through
PhD candidate at Cancer Institute, giving genetics can also be saved through regular
additional support to her research findings health checkups, early screening and also
with computational evidence. For that, I
performed some bioinformatics tasks such as appropriate treatment.
molecular docking, generation of heat maps Is there a way we can protect ourselves
using R programming and meta-analysis etc. from being affected by cancer by making
We wanted to prove her findings of using changes to lifestyle, food habits and
Riboflavin in the treatment of Oral Cancer environmental protection?
(where it highly interacts with MMP-1, MMP- Yes, we can protect ourselves by following a
3, MMP-9).
healthy lifestyle, like keeping ourselves fit
The project on cervical cancer was a CPCL through regular exercises, eating healthy food
funded project for screening and treating of (especially by avoiding spicy, oily and fast
HPV infected women in the community and foods), routine health checkups, avoiding
to study the properties of HPV-16 and HPV- habitual smoking and drinking and by
18, the most common strains of the virus to minimizing the exposure to pollution and
cause cervical cancer, at the genomics and impurities from the environment.
proteomics level. The aim of the project was Recently there has been this pandemic
to develop a self-sampling kit after caused by SARS-CoV-2. Among the
understanding the properties by using LAMP vulnerable group are said to be cancer
(Loop mediated isothermal Amplification patients. Do you have any anecdotes related
technique).
to this?
We see more and more incidences of cancer It is because that these viruses are virulent
in the world. Can this be reversed? Or is it strains affecting people who are exposed to
like the genie out of the bottle that cannot these viruses through environment and other
be contained?
sources. As cancer patients are already low in
As we can see, the number of cancer cases and immunity, they are affected easily as these
deaths are increasing in the world. This is due viruses can directly cause DNA damage and
to two main reasons: one being the increase in disrupt the regulation of the cell.
population and the other being aging. Not all
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Every field of research grows by expanding I am also pursuing a one-year post graduation
the frontiers. What is the next challenge in course in Cheminformatics and Drug
cancer biology? What is the next challenge Designing through distance education for
to be surmounted? which I have to do some assignment modules
and this lockdown period was helpful in
The global challenge would lie in improving finishing them.
our understanding of the immune system and
its role in cancer. This would help in Would you like to share your future goals?
development of new immunotherapies, and
the more effective usage of therapies which My future goal is to complete my doctorate
studies in which I would like to work in the
are already available. The next challenge is to field of cancer or any CNS diseases so as to
create novel tumour vaccinology approaches aid in healthcare department and for the
that establish or enhance successful immune welfare of the society. Later on, would like to
responses.
enter the teaching field where I can share my
What would provide succour when Sakthi knowledge and experience to the future
searches for (i) Humour (ii) Solitude (iii) generation.
Introspection (iv) Entertainment (v) Hobby
Your advice to those who plan to follow
Humour – movies, comedy shows your footsteps?
Solitude – Music, Books
Introspection – Meditation My simple advice would be that anything and
everything we do should be done with passion
Entertainment – Outings, Playing games with and interest. Always try to get into deeper
family members insights of what you learn and understand
Hobby – Singing, Dancing, Playing guitar and completely. Never limit your thinking when
keyboard
you enter into the field of research and always
21 days of lockdown. How did you make have a broad mind. Hard work and sincerity
use of the downtime (assuming you had are the key to success.
some)?
I am taking up some online free courses in
machine learning, NLP and Data Science.
Interviewed By
Rithika Suresh
Associate Editor
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Our very clever Odin is taking part in a quiz competition. Though he is good at oncology
himself, this brain wrecking quiz is getting on his nerves and he needs a team mate who
can be a multi-specialist.
Can you be one?
Well the host, Editor Montgomery thinks you do not have the occult. Prove him wrong by
answering the questions and don’t forget to mail them to [email protected]
1. A characteristic prognosis of colorectal cancer is blood traces in the stool. No test
better than this can detect it. Be a lab technician.
2. Born from B lymphocytes, these cells with CD15 and CD30 are unique to Hodgkin’s
disease. They are multi-nucleated and have owl’s eye appearance when viewed under
microscope. Be a histopathologist.
3. PEL - Ebstein fever, where the patient suffers from periodic occurrence of fever that
runs for a week or two and goes through a cyclic increase of temperature followed by
its decrease, is restricted to this cancer. Make the diagnosis.
4. The history of cancer takes us back to 3000 BC and is written in the texts of X which
belongs to a textbook of trauma surgery. The mighty cancer was not coined to be the
word that it’s referred as now, yet it records 8 cases of tumors or ulcers of the breast.
It was labeled as incurable. Find X, which originates from the land of mummies. Be
a bibliophile.
5. Hormone therapies, characterized by the use of hormones or hormone receptor
antagonists like tamoxifen and other aromatase inhibitors are practiced widely for
cancers of reproductive organs. The therapy marked its birth when Y performed
oophorectomy in advanced breast cancer after observing that the test rabbits stopped
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producing milk after the elimination of its ovaries. This was done in the 19 century,
before the discovery of hormones which makes him the one to have laid the ground
for modern hormone therapy. Get your historian self out.
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6. A rare endocrine tumor, with non-β isletic origin induces a plethora of vasoactive
intestinal peptide. The manifestation of this is diarrhea with acidosis, dehydration,
hypotension and other conditions. Be an etiologist.
7. This cancer occurs in children with a majority of no congenital abnormalities, while
sometimes may be due to WT1 or WT2 gene mutations. This tumor has a nephrogenic
origin that does not develop when the infant is in the mother’s womb and can lead to
Denys-Drash syndrome. Be a peds surgeon.
8. A possibility of the long awaited cure for breast cancer is here. A research that took
place in London found that it is not a drug or a hormone, but the cells of our own
body. It is a unique type of T cells that is present in the breast tissue itself. This opens
a doorway in the quest of finding a cure for breast cancer. Be an immunologist.
Answer for the Omics Edition’s Grey Matter
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Winners of Omics Edition’s Grey Matter
Vignesh K, IV BT-B Anantha Narayanan V, III BT-A Abhinav S, III BT-B
Questions courtesy
Anbarasi R
Senior Editor
&
SagayaKriti L
Editor-in-Chief
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Staying strong to fight back
Michael was this sensible guy who always put himself in other’s shoes before deciding who
and what they are. He was always kind to whomever he met to understand and help them
fight evil that comes and haunts everyone. Little did he know that an evil was waiting to
haunt him for the rest of his life (it never is that hurtful or haunting unless it occurs to one
self no matter what a great deal of swashbuckler one is). His body was failing him, his pain
unbearable, his thoughts unsettling to a point that he lost all his hope, he wished nothing but
death upon himself for a brief moment until a wild fire from the hearth made him ready to
face it. “How was that possible?” made everyone curious. A malady as deadly as cancer
always comes with a grim reaper to take your life with him. Yet he stood up to fight, to
never give in, a thought that changed him forever, a thought that didn’t come overnight to
him but took him days and nights to understand. He was determined enough to fight at all
cost to fight back the grim reaper so much so that he failed to take him back with him.
Michael stood tall and strong to smile back at the death thoughts, to fight for what he
deserved, to fight back for all he had, to fight back to get all he wanted. To this was life
happy to see a soul fighting with the mere thought that fighting strong alone and through
wit and will power can change one's path. Fighting back is not that easy but standing tall
against a deadly disease be it as simple as accepting it and moving forward with the
treatment and its monstrous after math is not a child’s play. You may lose or win this battle
but the war you are fighting will eventually be won.
Our Motivator
Priyadharshini R
Senior Editor
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Biopsy
Ever wondered what exactly a biopsy is and what the docs do to unravel the mystery? Well,
it’s now time to know that.
Cancer is indeed “The Emperor of All Maladies” as Siddhartha Mukherjee calls it. The crazy
crab is an opportunist that feeds on toxins, free radicals, foreign matter and mutated genes in
our body and grows to extend its filthy claws to various parts away from the origin after getting
bored of preying the same tissue. The key to kill it is to take it from the water and get its gills
dead dry. The first step to do that is to spot and trap it!! And that’s what a biopsy does.
Not every pain or mole is a cancer. That be told, after running a few labs for biochemical
screening and ruling out other possible conditions, the doc would order for MRI or CT scan or
Ultra sound depending on the tissue concerned. Upon suspicion from the tests and spotting a
lump in the scans, the doc recommends a biopsy.
A biopsy is taking a tissue from the affected area and examining it because you would want to
know how the crazy crab looks like, how it has fed off you, how far it has stretched its claws
and to know if it has reproduced. There are different types of biopsy techniques depending on
the tool and the affected area/organ.
The types of Biopsies are:
1. Needle Biopsy:
Guided by imaging techniques like CT scan, MRI scan or Ultrasound, needle biopsy is
simply inserting a needle to collect tissue. The different types of biopsy are:
❖ Fine Needle Aspiration Biopsy: A minimally invasive technique where a very thin
needle attached to a syringe and collects fluid and cell samples.
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❖ Core Needle Biopsy: This method is just like Fine needle method but just that a larger
needle is used to remove larger tissue sample.
❖ Vacuum Assisted Biopsy: In this case the doc uses a specific type of needle with
suction to collect more sample in one-go and reduce the amount of times the needle
has to be inserted to get the required amount of sample.
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2. Skin Biopsy:
❖ Excisional Biopsy: When the tumor is small and visible to the external eye, skin
or under the skin, the process of excision is done wherein the entire lump is
removed.
❖ Punch Biopsy: A small circular tool is inserted and the tissue below the skin is
removed.
3. Endoscopic Biopsy:
Endoscopic method uses a thin tube with a camera at one end to see abnormal areas.
This tube also contains special tools to collect tissue sample and is inserted inside
through mouth, rectum, urinary tract or any small incision. This method is often used to
collect sample from bladder, gastrointestinal (GI) tract.
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4. Bone marrow aspiration and biopsy:
Bone marrow aspiration and biopsy is used when fluid and solid tissue respectively are
to be removed with a needle. This is used to diagnose blood related cancers.
In case of suspicion of lymph node involvement, a biopsy of lymph node in the periphery
of the cancer margin is done following a Sentinel node mapping.
5. Sentinel node mapping and biopsy:
Sentinel node is the first lymph node that drains the primary tumor. Sentinel lymph node
mapping is a surgical procedure that employs use of dye to locate, excise and biopsy the
SLN to look for metastasis. If any mass or lump detected, it is biopsied.
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What follows the sample collection in biopsy?
Once the doc removes the required tissue sample using any of the above methods, the sample
is preserved in formalin (usually).
First the gross examination is done, in which abnormalities, visible to the naked eye, such as
size and other morphological features are reported.
Then, the sample is cut into sections (permanent or frozen) and is placed on a slide or is
smeared on the slide. In order to differentiate and view better, the sample is stained using dyes
(H&E – to differentiate nucleus from ECM and cytoplasm respectively) and viewed under
microscopic lens.
Upon viewing and diagnosis, a pathology report is made. It contains:
Type of cell involved.
Arrangement of cells.
Size and shape of cell, organelles and nucleus.
Abnormality if any.
STAGING:
Staging is the following step that helps describe localization, angiogenesis, migration and
metastasis.
TNM Staging System is commonly used for most types of cancer
➢ T - details on primary Tumor
➢ N - if the tumor has spread to the nearby lymph Nodes
➢ M - Metastasis (spread to the distant parts of the body) T along with a x or 0 to 4
describes the size of the primary tumor.
o Tx- Cannot be measured
o T0- Primary tumor cannot be found.
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o T1- T4 indicate increase in sizes. The higher the T number, the larger the tumor.
Similarly, N is represented by
o Nx - cannot be evaluated
o N0 - not spread to the nearby nodes
o N1-N3 indicate size, location, and the number of nearby lymph nodes affected by
cancer.
o Also,
o M0- No spread
o M1 – Cancer has spread to the distant parts of the body.
Other factors also help in diagnosing the stage of cancer:
➢ Grading: Grading is based on how abnormal the cells look under microscope. For
instance, in low grade cancers, cells are well differentiated but that is not the case with
higher grade cancers as the cells are poorly differentiated.
Eg: Standards for breast cancer follow Eiston – Ellis or Nottingham grading and for
prostate cancer follow Gleason grading system.
➢ Tumor markers: Tumor markers, or biomarkers, are usually proteins found at higher
than normal levels on the surface of cancer cells or in the blood. For many types of
cancer, tumor markers can help figure out how likely the cancer is to spread and help to
customize the best palliative treatment options.
➢ Tumor genetics: There are techniques like PCR, LAMP to determine the genes involved
in cancer. This may help predict if a likely metastasis is to happen and to give proper
curative care.
The details of TNM and the other factors are collectively considered to report a stage of cancer.
The stages of cancer are I, II, III or IV. Stage I indicates that the cancer is at a preliminary state
and Stage IV indicates that the cancer is highly advanced. There is also a Stage 0 which says
the cancer is in-situ, that is, the tumor is very small and is still in the place it started.
So that’s how a biopsy is done and the results interpreted. Next time you need not surf to
completely understand what a biopsy is! Worth the time, wasn’t it?
Brought to you by
Shampavi B
Associate Editor
&
Sagaya Kriti L
Editor-in-Chief
Click on the hyperlinks to jump into our knowledge fountains.
29
30
I started my career as a junior doctor in the arena of medicine. I was inclined to become a
doctor because my father was a doctor, maybe. He wanted to bring a breakthrough weight loss
programme in Hope Hospital in London back in his times. He always used to tell this joke,
“We hope to see less of you”. He is a funny man, I thought. It's interesting how this joke
influenced my career, and opened my eyes to the dreams of others. Yes, everyone hopes to see
the less of us, doctors, most of the times. Everyone wants to see themselves in less agony, less
illness and less pain. Hematology sparked a desire in me. It exposed me to people from various
walks of life lying in bed suffering from leukemia and other types of cancer. I wouldn’t want
myself to endure the agony of my body turning against itself. That’s what cancer is. Your cells
turning against you like how Brutus stabbed Caesar’s back.
John and Sarah, two of my patients, have always seen more of me. John, a man in his forties
with a young family, had a type of lymphoma that always found a way to come back into his
body. He had undergone chemotherapy for several years and he was suggested to have a bone
marrow transplant. The bone marrow of a patient is substituted with that of a healthy donor
and for John, it worked despite making him weak in the process. Sarah, on the other hand,
lacked a chunk of luck. She was diagnosed to have leukemia, a type of blood cancer at the age
of 14 – the age when most of us were playing with friends on streets. Alas, the bone marrow
transplant had caused a severe inflammatory reaction that lead to her end. The bone marrow
transplant has proven to be a fair chance of winning or losing the battle against cancer.
Our body has T cells and B cells that constantly watch out for the foreign invaders entering
our body and guard us against their possible attack. Brilliantly, cancer cells evade this
surveillance and go incognito. So why not help the domestic police force of our body? The real
challenge that comes into picture is the question, “How to help a compromised immune system
to recognize the hidden villain?” The answer made its way. My crew and myself developed a
kind of immunotherapy called as “Chimeric Antigen Receptor T-cell Therapy or the CAR-T
therapy”. The CAR-T cells act like the targeting pointer found in the sniper of our police force.
The CAR-T cells are prepared by obtaining blood from the patient and separating the T-cells.
A new gene is incorporated into the T-cell that encodes the protein called CAR (Chimeric
Antigen Receptor). This provides a new capability to the T-cells to recognize the tumor cells
using the best properties of a B-cell. These CAR-T cells can now be injected into the patient’s
vein post safety testing in the lab.
31
The CAR-T cells, which now have the ability to recognize tumor cells, bind to them and
undergo rapid multiplication upon encountering the site of cancer. At first, a small dose is
administered after a little bit of chemotherapy to prevent rejection and is followed by close
monitoring of the patient since any unfavorable inflammatory reaction would be fatal and it
needs to be dampened. The CAR-T cells slowly decrease in number after their job is done and
a few cells may linger providing a long-term protection. This therapy is currently under
clinical trials. My vision is to provide this therapy in an enhanced manner with slight
modifications on the T-cells in such a way that a batch of CAR-T cells obtained from healthy
donors can be ordered just by referring the patient’s biopsy and his gene sub-type. Just like
ordering blood from a blood bank! The dream of cancer patients suffering less is becoming
closer to reality in my eyes. Sometimes, a joke can be a beginning for magical dreams come
true.
Inspired from the dreams of patients who hope for a miracle in their phase of life with cancer,
all the while lessening their pain and suffering is, Dr. Robert Weinkove, Clinical Director,
Malaghan Institute for Biomedical Research, Wellington.
Do click here to witness the dynamic Dr.Rob throw light on the promising future CAR-T cell
therapy holds!
Narrated by
Anbarasi R
Senior Editor
Click on the hyperlinks to jump into our knowledge fountains.
32
33
The curse & cure!
"Cancer is like a teeter-totter, sometimes deadly diseases- cancer. Using 3-D
you gotta go down to go back up", says imaging, the researchers have diagnosed
Joe Andrew. Cancer - this 6-letter word an aggressive type of cancer called
is responsible for every '1 out of 6 deaths' osteosarcoma in a foot bone, belonging to
across the globe. a human relative who died in Swartkrans
Cave between 1.6 and 1.8 million years
Human beings and other animals have had ago.
cancer throughout the recorded history.
People back those times considered The abnormal growth pattern of bone
cancer as a bringer of lament and named tissue, including a distinctive,
it as a ‘Curse of the GODS' owing to the cauliflower-like external appearance, led
almost null chances of cure and its the team to diagnose the condition as
fatality. The oldest description of cancer osteosarcoma, which today afflicts mostly
was discovered in Egypt and dates back to children and young adults.
about 3000 BC. It’s called the 'Edwin Other studies by numerous scientists and
Smith Papyrus' and is a copy of part of an researchers also state the growth in a
ancient Egyptian textbook on trauma vertebra from a 1.98 million-year-old
surgery.
juvenile skeleton of Australopithecus
Ancient Greeks first identified cancer as a sediba, discovered at a site called Malapa,
specific illness. It appears that the Greeks also tend to be one of the oldest cases of
had a better knowledge and awareness of cancer. Prior to this discovery, the oldest
cancer. The term gets referred in the known benign growth was in the 120,000-
Hippocratic Corpus- a text said to have year-old rib of Neanderthal, excavated in
been written by the "Father of medicine", Croatia.
Hippocrates, between 410 and 360 B.C. A group of scientists recently developed
The Roman physician, Celsus (28-50 BC), kinase inhibitors-small molecular
later translated the Greek term into compounds that go after the protein
cancer, the Latin word for crab. Galen kinases, whose dysfunction is involved in
(130-200 AD), another Greek physician, the explosive growth and proliferation of
used the word oncos (Greek for swelling) cancer cells. That is, "turning OFF” the
to describe tumors.
Switch of cancer cells. The new research
In the fossil-rich region of South Africa, attacks cancer from the opposite side of
known as the Cradle of Humankind, the equation, turning on cancer's "off
scientists have discovered the earliest switch" by stabilizing protein
known case of one of the world’s most
34
phosphatases, whose malfunction Present day advancements have brought
removes a key brake on cancer growth. us one step closer to winning the battle!
For whatever it takes, mankind is never
Every "Curse has a Cure" and we've going to stop until it has found what it
grown up believing that all along, starting takes to defeat this killer disease and
from the long-lost civilizations and their make this world a better place to live in.
aesthetic culture to the modern lifestyle
that exists today.
Heemanthz Sai Krishna, III Year, BME-A
Disease of civilization
It had been recognized that there are According to the WHO, people living in
certain fundamental changes in diet and high income countries and middle-income
lifestyle that have occurred after the countries predominantly die of chronic
Industrial Revolution and the Modern lifestyle diseases. In low income
Age. They are too recent, on an countries, people often die of infectious
evolutionary time scale, for the human diseases, such as malaria, and influenza.
genome to have completely acquainted. Every country has come a long way in
This mismatch between our ancient learning how to prevent the infectious
physiology and the modern diet and diseases. We should all be grateful that we
lifestyle underlies many so-called don’t have to contend with malaria or
diseases of the civilization, including dengue on a daily basis.
coronary heart disease, obesity, Cancer happens for numerous reasons.
hypertension, type 2 diabetes and cancers, The mismatch between our ancestral
which are rare in populations that are environment and the current environment
more “old fashioned”. It is therefore that we live in is one of the reasons why
suggested that the adoption of diet and we get cancer. It happens because our
lifestyle that mimic the beneficial evolved cancer suppression systems
characteristics of the pre-agricultural haven’t been able to keep pace with the
environment is an effective strategy to speed of change in our lifestyle. And it
reduce the risk of chronic degenerative happens due the different types of
diseases.
exposures that we have in the modern
35
world such as sun, smoking, chemicals alters our physiology, our hormone levels,
and even too many calories that our metabolism, insulin regulation and
overwhelm our body’s ability to suppress can increase inflammation.
cancer.
The adoption of diet and lifestyle that are
For example, a certain amount of sun very different from what shaped the
exposure for our bodies is required to human genome for more than 2 million
function normally. The nature of skin has years is an important factor in the
evolved to suit the climactic types of their widespread prevalence of chronic
ancestry. But when light-skinned degenerative diseases that are epidemic in
individuals living in temperate regions western countries. Focusing on an
visit areas that are close to the equator (for isolated dietary or lifestyle variables is
either official visits or vacation), they are not an appropriate strategy for prevention.
at a higher risk for skin cancer because Cancer is a disease of (changing)
their skin lets in more radiation from the civilization.
sun which damages the DNA eventually Our susceptibility to cancer is simply part
resulting in cancer. Smoking is another of being a multicellular organism made of
reason that increases cancer risk. The Cancer occurs because cells in our bodies
smoke contains chemical carcinogens that evolve at a rate faster than our cancer
damages DNA leading to more mutations.
suppression systems. So, cancer is partly
We eat much more and exercise much less a disease of modernity, but it is also an
than our ancestors ever did. This means ancient disease, one with roots that go
that we have a huge amount of excess back deep into our evolutionary history as
calories that our bodies have to store and multicellular organisms
manage. When we have higher body fat, it
Rakssha Ramesh, IV Year, BT-B
Cancer
Cancer is a malignant disease around revolving. The characteristics of
which an enormous number of uncontrolled proliferation and spreading
researches, discoveries and debates are (metastasis) via blood vessels and lymph
36
vessels to various parts of the body makes Resistance against therapy
the relapse free survival and overall Various mechanisms are attributed to the
survival difficult. This is because the failure of anticancer therapy. These include
metastasized cancer cell has entered a drug inactivation, increased drug
quiescent stage where it doesn’t metabolism, altered drug target, apoptosis
proliferate and remains dormant in some inhibition, high expression of multidrug
of other parts of the body while retaining resistance pumps (ABC transporters),
the characteristics of the cell of origin. epigenetic alteration (DNA methylation and
For instance, a prostate cancer cell
metastasized to bone will retain the histone modification), miRNA alteration,
enhanced DNA repair and gene amplification
characteristics of the prostate cancer and and autophagy. For instance, the drug
doesn’t have the characteristics of the metabolism is enhanced by CytochromeP450
bone cell. The dormant cell in the that leads to drug inactivation; Drug
secondary site has stem cell like inactivation by high Glutathione S
properties which make it more difficult to Transferase enzymes; mutation in the drug
be eradicated by normal chemotherapy.
target protein lower the treatment efficacy;
The overall process of metastasis and the Gene amplification and defective miRNA
survival of cancer cells is mediated by lead to increase in onco-proteins level.
tumour microenvironment. For example,
cytokines secreted by the surrounding tissues Some ABC transporters serve as drug
efflux pumps in cancer cells. These
will aid in the process of epithelial to proteins are also found to be expressed in
mesenchymal transition where the cancer both normal and cancer stem cells. These
cell loses the attachment proteins and make them more resistant to
becomes motile. This motile cancer cell will chemotherapy drugs. Also, clonal
evade the immune cells and the shear blood expansion in cancer lead to the survival
force through various mechanisms and gets of particular cancer cells withaltered
settled in a new site by undergoing genetic characteristics after the
mesenchymal to epithelial transition. This treatment.
process is supported by a hypothesis called
‘Seed and soil hypothesis’ which states that a Autophagy is a mechanism which has
cancer cell (seed) needs a suitable site both cytotoxic and cytoprotective effects.
(congenial soil) to grow. The selection of In cancer, acidic environment leads to
secondary site is chiefly dependent on pro-survival mechanisms including
chemokines secreted by the autophagy where drugs are eliminated
microenvironment cells. from the cell.
37
To add on, the recent sensation are some of the active areas of research
chloroquine increases the pH inside the that have to be focussed to improve the
cell, thereby inhibiting autophagy.These survival of the patient.
Naveenraj, IV Year, BT-A
The second life
Cancer, “An Emperor of Maladies”, is
intimidating because of the procedures To vanquish the setbacks of the
one is subjected to during the course of
his/her treatment. Before I explain why I conventional treatment, scientists have
quoted this article as, “Second Life” I emerged with various treatments such as
would like to draw attention on the fact, targeted therapy, immunotherapy etc.
to why cancer treatments are a The effectiveness of these treatments is
nightmare. achieved when the key targets are
destroyed, increasing the competence of
Currently the treatment given to patients nano-particles being used to enhance the
are broadly classified into three sub therapeutic efficiency of targeted therapy
classes:
and immunotherapy along with,
• Surgeries increasing the survival rates.
• Chemotherapy Nanoparticles in targeted cancer
• Radiation therapy treatment:
These treatment procedures subject the Nanoparticles have been used in cancer
patients to a lot of trauma therein making treatments to increase the
them mentally and physically weak, pharmacokinetic of the drugs and make
scared thereby leading to depression and the drug delivery more effective.
eventually death. These treatments do Selective delivery of nanotherapeutic
not ensure complete eradication of the platforms depends primarily on the
cancer cells, increasing the possibility of passive targeting of tumors through the
recurrence. The treatment protocol not Enhanced Permeability and Retention
only destroys the cancerous cells but also (EPR) effect.
causes substantial damage to the healthy
neighboring cells in the clinical border as Nanoparticles in immunotherapy:
well. Immunotherapy has been one of the most
promising cancer treatments at present. The
38
therapy has various approaches which I'm amazed reading these boundless
include cellular therapies and check point wonders of what few tiny particles can
inhibition. At present, nano particles have do.
been employed in immunotherapy for the Therefore, as a small thought to all my
delivery of immunomodulatory or fellow enthusiastic cancer biologists,
immunostimulatory compounds in drawing in a notion that, if a small
accordance with chemo or radiation particle can do great wonders, we, being
therapy. Nanoparticle vaccines are also its masterminds, can infuse their work
being designed to raise sufficient T-cell with the amazing skill-set to enable a
response to eradicate tumors, through co- better life for the warriors who battle
delivery of antigen and adjuvant.
their lives against this deadly disease.
The figure depicts the complex pathway Let’s join hands to ensure them a very
involved in cancer immunotherapy; here happy “Second Life”.
nanoparticles play a vital role at multiple
points along the pathway.
Shreaya B, II Year, BT-C
39
MaTe for Rescue
Contaminant mess
Max: How long do I need to type....to get done with this introduction! (groans)
Max and Teju are done with their project work and are starting off with their theses.
Teju: Stop cribbing. Start working. (Focusses on her word document)
Max: No use! (sigh)
Priya storms into the class room with Dia and Adi trailing behind her. They are
returning from the cell culture lab.
Priya: If I happen to get hold of that person, he is done once and for all. The RPMI
media is really costly and we can’t afford to waste it like this. (bangs her fist on the
table)
Dia and Adi look really worried and look at each other and try to calm her down.
Max startled by that sound pulls Dia aside and asks,
Max: What's wrong guys? What happened?
Dia: What do I tell you? You do remember that she is working on this very important
departmental project with juniors, right? The one with the HeLa cell lines to study the
effects of an anti-neoplastic drug?
Max: Yes, I do. Go ahead.
Dia: After 8 passages going well, with them being done with the dosage studies and
Western blot analysis of pathways involved, they are now at an all important stage to
carryout flow cytometry to spot the significantly upregulated receptors. But it is only
now that someone has deliberately been contaminating the RPMI media or FBS, not
so sure, and you know they are costly.
Max: They are definitely very costly.
Dia: Microscopic images of the HeLa cells revealed black spots, which made them
check the carbon dioxide supply to clear out that possibility as only recently it was
replaced. So, it’s gotta be only media contamination but God knows how!
Max: Shoot!
40
Dia: She has been really worked up with it.
Meanwhile, Teju comes out of the class.
Teju: Hey Dia! Are you done with your thesis?
Dia: (clearly absentminded) Yes, I guess.
Teju: Cool! Max hand me over your copy of the introduction or just mail it to me I'm
going to get the printouts.
Max: (fumbles) I haven't finished it. I'll take care go ahead.
Teju: You........ (voice trails off)
Teju exits immediately while clearly shouting at Max for being irresponsible.
Max: I will handle that later, Dia tell me for how long has this being going on?
Before Dia could answer, Adi steps in.
Adi: Dia, Priya has been calling you just see what it is.
Max: Adi, atleast you tell me what's happening exactly and since when
Adi: I have got pictures of the contamination and it has been happening everytime
they seed new plates. The next day it is doomed. This is the 4th time that it has
happened!
Max: Send those pictures over to me. I shall see what I can do.
Adi: It means a lot. Thanks!
Teju returns to class with the printout with a morose expression on her face. Clearly
unaware of what happened, Max comes and strikes up a conversation.
Max: Did you know what just happened....
Teju: Don't utter another word. I'm not ready to listen to anything.
Max is caught off-guard and doesn't know what to say
Max: What happened?
Nithya, who is a common friend of both of theirs calls Max aside
Max: What happened there? Why is she upset with me?
41
Nithya: You haven't turned in your introduction pages and when Teju went to submit
hers, ma'am shouted at her because she couldn't even get her best friend to finish her
work.
Max: This is really unfair; I will talk to Josephine ma'am.
Max enters into the staff room and senses a commotion. Two or three other staffs have
been crowding her guide's desk and she decides to eavesdrop on them.
Josephine ma’am: I'm really worried Lakshmi ma'am, the cells are being contaminated
and we have to submit the report in another 10 days.
Lakshmi ma'am: I understand. Why don't you do those plates on your own and let the
kids do their thing so that we can catch the real culprit and even the work won't be
affected.
As Max hears shuffling inside, she hides near the partition and Josephine ma'am leaves
hurriedly.
Max turns to leave, and comes face to face with Shyam sir,
Max: Sir, I got scared.
Shyam sir: Maxine, I know you are upto something but don't forget I'm supposed to
correct your thesis on time.
Max who knew that Shyam sir was one of the friendliest staffs in the department and
would let her off the hook for any mischief.
Max: Yes sir! Sure sir! Right away sir! (she scurries away to her classroom)
Will Max find the culprit and make up things with Teju? Will she complete her thesis
on time? Wait for the next issue of MaTe for rescue.
Rakshana R, IV Year, BT-B
42
Cancer
A familiar stranger; as they invigorate, clinging onto my creepers of existence.
The body of mine has become the battleground,
Of what both the allies fight for their triumph,
To reign my rhythmic heart beats;
Either to sing the song of life, or the final notes my lungs loathe not.
As the birds chirp on the window pane, along the synchronizing notes of the monitor,
The music and dance, foreigners in me.
They cause multiple entourages of themselves; the bed I lay myself often,
Either a resting bed of resuscitation or the reserved coffin - is yet to be known.
Beyond the glamour of my body ruined;
And over the final threads of my dying ambience,
I am yet to find the beauty of what my loved ones; heart bore; as my heart pumps a
dying beat often.
How unknown or unsolicited,
The stranger unraveled into me; my soul shall not demise as my blood is taken,
For the guests’ greed in me.
As the hands of mine are held, by those who long for my return;
Envisioning the hope, I had lost, I shall last for the undying trust for me.
Sowmia Narayan Sridhar, II Year, BT-C
43
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