CONTENTS
Author: Dropcho EJ
Address: Department of Neurology, Indiana University Medical Center, Indianapolis
46202, USA. dropcho@iucc.iupui.edu
Source: J Neurol Sci, 153(2):264-78 1998 Jan 8
Abstract
Several neurologic paraneoplastic disorders are believed to be caused by an
autoimmune reaction against antigen(s) co-expressed by tumour cells and
neurons. Of the paraneoplastic syndromes, the evidence for an autoimmune
etiology is strongest for the Lambert-Eaton myasthenic syndrome, in which
autoantibodies downregulate voltage-gated calcium channels at the presynaptic
nerve terminal. For other syndromes, including cerebellar degeneration,
multifocal encephalomyelitis, sensory neuronopathy, limbic encephalitis,
opsoclonus-myoclonus, stiff person syndrome, and retinal degeneration, the
autoimmune theory is supported by the presence of specific antineuronal
antibodies. These antibodies serve as a useful diagnostic tool, but their
actual role in causing neuronal injury and clinical disease remains unclear.
Further understanding of immunopathogenesis awaits successful experimental
models. Among different syndromes, a varied proportion of patients shows
neurologic improvement with immunosuppressive treatments; it is likely that
many patients have already suffered irreversible neuronal injury at the time
of diagnosis.
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Language
Eng
Unique Identifier
98170833
------------------------------------------------------------------------
MESH Headings
Animal ; Autoimmune Diseases PA/PP/PX ; Human ; Nervous System Neoplasms
PA/*PP/PX ; Paraneoplastic Syndromes PA/*PP/PX
------------------------------------------------------------------------
Publication Type
JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
ISSN
0022-510X
Country of Publication
NETHERLANDS
Author: Jaeckle KA
Address: Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA.
Source: Curr Opin Oncol, 8(3):204-8 1996 May
Abstract
Recent progress in the understanding of the paraneoplastic neurologic
syndromes has included further deliniation of the clinical syndromes and their
treatment, attempts at standardization of the diagnostic nomenclature,
investigations of pathogenetic mechanisms, and molecular characterization of
the paraneoplastic antigens with implications as to their biologic relevance.
Despite more than 30 years of investigation, the pathogenesis of these
presumably autoimmune conditions remains unclear. Furthermore, no effective
therapy has been identified for these conditions, with the possible exception
of the opsoclonus-myoclonus ataxia and Lambert-Eaton myasthenic syndromes.
Future investigations must focus on the disrupted genetic regulatory events
involved in generation and propagation of the autoimmune response, antigen
presentation and processing; target cell destruction, and consideration of
alternative pathologic causes. Effective management strategies are most likely
to develop from a better understanding of the disease pathogenesis, the
development of animal model systems, and a creative look beyond the usual
therapies employed in autoimmune conditions.
Language
Eng
Unique Identifier
96397931
------------------------------------------------------------------------
MESH Headings
Antibody Specificity ; Autoantibodies IM ; Autoantigens GE/IM ; Autoimmune
Diseases CL/DI/*ET/IM/TH ; Human ; Nervous System Diseases DI/*ET/IM/TH ;
Nomenclature ; Paraneoplastic Syndromes */CL/DI/IM/TH ; Syndrome
------------------------------------------------------------------------
Publication Type
JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN
1040-8746
Country of Publication
UNITED STATES
Author: Lucchinetti CF; Kimmel DW; Lennon VA
Address: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Source: Neurology, 50(3):652-7 1998 Mar
Abstract
Type 1 antineuronal nuclear autoantibody (ANNA-1, also known as "anti-Hu") is
a marker of neurologic autoimmunity that is highly associated with small-cell
lung carcinoma (SCLC). To determine the spectrum of symptoms and signs as well
as the frequency of cancer in adult patients who are seropositive for ANNA-1,
we reviewed 162 sequential patients (67% female) identified as ANNA-1-positive
in a comprehensive immunofluorescence screening test. In 21% of these
patients, the antibody test requested by the physician was not ANNA-1. By the
end of the follow-up period, cancer had been found in 142 patients (88%). Ten
of these lacked evidence of SCLC (4 had prostate carcinoma, 3 breast
carcinoma, 1 both prostate carcinoma and melanoma, 1 lymphoma, and 1 squamous-
cell lung carcinoma). Of the 132 patients (81%) with proven SCLC, 17 had one
or more coexisting malignant neoplasms (6 had renal carcinoma, 4 another lung
primary carcinoma, 3 prostate carcinoma, 3 breast carcinoma, and 4 assorted
neoplasms). The diagnosis of SCLC in 128 patients (97%) followed the onset of
paraneoplastic symptoms. SCLC was identified in 10 patients by chest MRI after
an equivocal chest radiograph or CT; in 28 by bronchoscopy, mediastinoscopy,
or thoracotomy; and in 7 at autopsy. Neurologic signs in decreasing frequency
were neuropathy (sensory > mixed somatic > autonomic > cranial [especially
cranial nerve VIII] > motor), cerebellar ataxia, limbic encephalitis,
polyradiculopathy, associated Lambert-Eaton myasthenic syndrome, myopathy,
myelopathy, opsoclonus/myoclonus, motor neuronopathy, brachial plexopathy, and
aphasia. Nineteen patients had a solely gastrointestinal initial presentation,
including gastroparesis, pseudo-obstruction, esophageal achalasia, or other
dysmotility. We conclude that seropositivity for ANNA-1 can expedite the
diagnosis and treatment of otherwise occult cancer in patients, especially
tobacco abusers, with varied neurologic and gastroenterologic presentations.
The search for SCLC should not end on discovering a different neoplasm.
Language
Eng
Unique Identifier
98180547
----------------------------------------------------------------------
MESH Headings
Adult ; Aged ; Autoantibodies *AN ; Carcinoma, Small Cell EP ; Cerebrospinal
Fluid Proteins AN ; Female ; Gastrointestinal Diseases IM ; Gastrointestinal
Motility ; Human ; Incidence ; Lung Neoplasms EP ; Male ; Middle Age ;
Neoplasms *EP ; Nervous System Diseases IM ; Paraneoplastic Syndromes *IM ;
RNA-Binding Proteins *IM ; Support, U.S. Gov't, P.H.S.
------------------------------------------------------------------------
Publication Type
JOURNAL ARTICLE
ISSN
0028-3878
Country of Publication
UNITED STATES
The Cancer Journal - Volume 11, Number 5 (September-October 1998)
The recent experience with biphosphonates and their application in cancer therapy seems to
be a case of serendipity. On the other hand, it might be the first in a series of similar
discoveries, which are not due to chance but to the systematic investigation of a
hypothesis which could hold for all progressive cancers?
http://www.infobiogen.fr/agora/journals/cancer/articles/11-5/edia.htm
Some Humans may be
Immune to Cancer
By Nicolle Charbonneau
HealthScout Reporter
TUESDAY, Nov. 3 (HealthScout) -- In cancer research, one of the hottest
fields of study involves immunology, the idea that the body itself can
fight off the disease. Building on animal studies -- specifically on
mice -- researchers have found the first evidence of naturally occurring
tumor immunity in humans.
Researchers at Rockefeller University in New York City have identified
tumor-specific killer T cells that can suppress or even kill specific
tumor cells in an extremely small percentage of the population. Their
findings appear in the new issue of the journal Nature Medicine.
To do this, primary researcher Matthew Albert, a biomedical fellow at
Rockefeller University and Cornell University Medical College, turned to
four patients suffering from a rare neurological condition called
paraneoplastic cerebellar disorder (PCD), which affects about one out of
every 1,000 women with breast or ovarian cancer. These women show an
extraordinary immune response against their tumors, often enough to
suppress or even kill the cancer cells.
But this apparent miracle has a terrible downside. This immune response
leads to the onset of severe neuro-degenerative symptoms. They can
include loss of motor control, leading to difficulty walking, or even
sitting up straight. In fact, two-thirds show neurological symptoms
before they're diagnosed with cancer.
These symptoms usually bring them to the doctor in the first place. This
brings an early intervention in cancer diagnosis, often catching the
disease in a beginning stage. At least 90 percent are diagnosed with
cancer while it's still limited. This compares to overall rates of 60
percent for breast cancer patients, and only 25 percent for those with
ovarian cancer.
Compared to the symptoms we experience when we catch a cold, for
example, "if you or I were to develop a cancer, and our body was able to
be effective in recognizing and killing it, we might have no symptoms
from it," says senior author Dr. Robert Darnell, the head of the
Laboratory of Molecular Neuro-Oncology at Rockefeller.
Patients with effective immunity to a cancer may never realize that they
have the disease, and would never approach a doctor who could then study
what gives that person immunity. "The patients that they really want to
study, where the tumor immunity is theoretically the most effective,
would be the least likely to end up in an oncologist's office," says
Darnell. That made the patients, with their obvious outward signs of
neurological degeneration, the best chance to identify and examine this
anti-tumor response.
When the researchers examined the women, they found antibodies for an
antigen called cerebellum disorder related protein 2 (cdr2), which for
reasons still not understood, exist in their tumors. But Albert's team
wasn't convinced that the isolated antibodies were responsible for the
immune response. Cdr2 proteins exist inside the cancer cells, and
antibodies shouldn't be able to reach them there.
So, they turned to the model that exists in mice, where tiny bits of
dead proteins are displayed on the surface of each cell. This allows T
cells to determine whether a cell is normal (and should be left alone)
or infected or foreign (and should be destroyed). So Albert and his team
went looking for the T cells that target the cdr2 protein. As it turned
out, the PCD patients "seemed to have them in spades," Albert says.
At that point, the researchers had the connection between these specific
killer T cells and naturally occurring tumor immunity.
For patients with PCD, the reprieve from cancer is a mixed blessing.
Normally, the brain is off-limits to the body's immune system, but not
for patients with PCD. Some unknown mechanism allows these
tumor-specific T cells to cross the blood/brain barrier, and there they
begin to attack neurons in the cerebellum, which also contains cdr2,
causing the loss of fine motor control. The patients lose the ability to
coordinate their arms and legs, have difficulty swallowing or speaking,
and are confined to bed or a wheelchair.
Some experience nystagmus, an involuntary rolling or twisting of the
eyes, which can cause dizziness and nausea. Through these devastating
symptoms, the patient remains completely aware and alert.
These destructive neurological disorders may now be the key to future
research in immunological approaches to cancer treatment. There have
been anecdotal reports that immunotherapy for melanoma can cause
vitiligo, an attack that leads to a blotchy depigmentation of the skin.
Although it's years away, "it's going to be something of incredible
importance," says Albert, adding that a crucial step in developing ways
to activate people's immune systems to specifically target tumors will
be to make sure the treatment doesn't trigger an autoimmune disease.
What To Do: For more information on this topic, check out on the
University of Washington web page on Immune Therapy for Cancer or this
Scientific American article about cancer and immunotherapy.
Copyright © 1998 Rx Remedy, Inc.
What's new at Memorial Sloan-Kettering Cancer Center
and its World Wide Web Site
---------------------
http://www.mskcc.org
====================================================
December, 1998
----------------------------------------------------
In This Issue:
*FEATURE: Dealing With Cancer Stress During The Holidays*
*NEW Bladder Cancer Overview*
*NEW Lymphoma Overview*
*Patients Should Check Hospital Expertise Before Surgery*
*Prostate-Cancer Predictor Found*
*Therapy Blocks Cancer Cells' Survival Signal*
*Laurance S. Rockefeller Makes Major Gift to MSK*
*Gov. Pataki Signs Health Insurance Bill Into Law*
*Symposium Focuses on Immune Response*
*Interview with SKI Developmental Biologist*
---------------------------------------------------
Welcome to Lately@MSKCC!
For many patients with cancer and their caregivers, holiday
decorations, songs, and family gatherings are the perfect
emotional medicine to take their minds off a condition that
has, otherwise, been at the center of their worlds. But as
much as the holiday season is a time of happiness and
togetherness for a lot of people, for some who are dealing
with stressful life events, such as cancer, it can be an
especially difficult time. Often, the expectation of joy
conflicts with a reality of physical discomfort, concern, and
fear.
If you are one of those cancer patients or caregivers for
whom the coming holidays are difficult, there are things you
can do to take control of your situation and experience some
joy during the holiday season. And if you know someone with
cancer, or someone who is caring for a cancer patient, there
are also things you might do to help make the holidays a
little easier for that person.
An important first step is to think about what is really
important to you and what you really need, and then make your
holiday plans around those priorities, says Karrie Zampini,
who heads Memorial Sloan-Kettering Cancer Center's
Post-Treatment Resource Program. By taking responsibility and
setting your own pace, you can keep the season from becoming
just a tiring string of commitments. Try to do only what will
make you feel happy. If you have cancer, you may not have the
energy to attend a lot of parties, or to host the big family
feast this year. If you're a caregiver, you may also not have
the time or emotional stamina to do these things. People will
understand if you ask another family member to host the
holiday dinner, or if you decline an invitation.
If you're a caregiver, remember that feeling good makes you
a better companion. Take some time for yourself this holiday
season. There's nothing wrong with accepting someone's offer
to watch your loved one for a while so you can see a movie
with a friend or go to a holiday party.
There are resources available to help you deal with the
stress that cancer can bring--now or at any time, adds Ana
Marchena, health education specialist at Memorial
Sloan-Kettering. MSK's own Post-Treatment Resource Program is
one source you can rely on if you're in the New York City
area. Elsewhere in the United States, groups like Cancer Care
Inc., a non-profit organization dedicated to helping cancer
patients and their families, also have counselors ready to
speak with you.
If you know someone with cancer, or someone who is caring
for a cancer patient, don't assume that he or she doesn't
wish to be included in your social calendar. Invite them to
your holiday gatherings, as you would if cancer had nothing
to do with their lives. Let them decide whether they'd like
to attend or not, and understand if they can't. If you do
have a cancer patient coming to your holiday dinner this
year, be sure to ask about possible dietary restrictions. You
might want to prepare a special plate for him or her. But do
include that person in your holiday.
Most of all, whether you're a cancer patient or caregiver,
try not to put too much emphasis on this one time of year.
"After all, there is something to celebrate in every day,"
says Ms. Zampini.
Recently, Cancer Care Inc. hosted a telephone conference
call for cancer caregivers on handling the holidays. For more
tips on how you can make this holiday season easier for
yourself, you can listen to a RealAudio recording of that
conference call. A link to the RealAudio recording will
appear on Cancer Care Inc.'s Web site in the next few days,
so you might want to bookmark this link and check back.
http://www.cancercare.org/audio/teleconferences.htm
WHAT'S NEW AT MSKCC.org
------------------------
*Bladder Cancer Overview*
About 54,400 Americans will be diagnosed with bladder cancer
by the end of 1998, but new therapies for bladder cancer and
improved diagnosis have led to a steady decline in deaths
from the disease since the early 1970s.
http://www.mskcc.org/document/WICBLAD.htm
*Lymphoma Overview*
You'll find information about different types of lymphoma
and their diagnosis and treatment in this new Cancer
Overview.
http://www.mskcc.org/document/WICLYMPH.htm
*Patients Should Check Hospital Expertise Before Surgery*
In a study published in the November 25 "Journal of the
American Medical Association," researchers from Memorial
Sloan-Kettering Cancer Center found that mortality rates were
40 to 80 percent lower in hospitals that had the most
experience performing a particular surgical procedure.
http://www.mskcc.org/document/PR981123.htm
*Prostate-Cancer Predictor Found*
If doctors knew how aggressive a given patient's cancer
might be, they could select the type of treatment likely to
be most effective for that patient. Center investigators have
recently pinpointed a protein that may do just that — one
that predicts whether a given prostate tumor might grow and
spread quickly, or take a slower course.
http://www.mskcc.org/document/cn981201.htm
*Therapy Blocks Cancer Cells' Survival Signal*
Dr. Gary K. Schwartz is evaluating a new drug therapy that
kills tumor cells by interrupting the signals that persuade
them to survive.
http://www.mskcc.org/document/CN981203.htm#chemo
*Laurance S. Rockefeller Makes Major Gift to MSK*
MSK recently received a significant contribution from
Laurance S. Rockefeller, Honorary Co-Chairman of the Center’s
Boards of Overseers and Managers. The gift not only supports
cancer research, but has the added benefit of preserving open
space along the banks of the Hudson River in Westchester
County, New York.
http://www.mskcc.org/document/CN981204.htm
*Symposium Focuses on Immune Response*
In an effort to comprehend better how the body’s own immune
system can manipulate, block, and attack tumor cells, leading
scientists from the United States, Europe, and Israel
gathered at MSK in October for the Eighth Robert Steel
Foundation International Symposium on cancer.
http://www.mskcc.org/document/CN981205.htm
*Interview with SKI Developmental Biologist*
"In my lab, we're studying the fruit fly to explore how a
cell's fate is determined. In other words, how does one cell
become a muscle cell, while another becomes a skin cell? How
does development proceed in a very reliable, reproducible way
from a single-celled egg to an organism with many different
cell types?" -Dr. Kathryn V. Anderson, Developmental
Biologist. Learn more about her work in this interview.
http://www.mskcc.org/document/CN981210.htm
------------------------
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