Nuno Miranda

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Nuno Miranda
Vírus e cancro
Vírus e cancro
O olhar do clínico
• Vírus como causa do cancro
• Vírus como complicação do cancro
• Vírus como tratamento do cancro
Vírus como tratamento do cancro
O
O cancro como doença infeciosa
d
i f i
• Primeiras provas de modelo animal por Rous
“In
In this paper is reported the first avian tumor this paper is reported the first avian tumor
that has proved transplantable to other individuals. It is a spindle‐celled sarcoma of a hen which has thus far been propagated to
hen, which has thus far been propagated to the fourth generation…”
C
Cancro cervical como doença infeciosa
i l
d
i f i
• 1840 Domenico Rigoni‐Stern publica que as f i d V
freiras de Verona raramente tinham cancro t ti h
,
ç
cervical, e a doença era muito comum entre prostitutas da mesma região.
In 1842, the Italian physician Domenico Antonio Rigoni‐
Stern noticed that nuns in Verona were more susceptible
Stern noticed that nuns in Verona were more susceptible to breast cancer than other women. Ruminating on what aspect of convent living might explain the phenomenon,
aspect of convent living might explain the phenomenon, he concluded that the nun's corsets were too tight. This explanation was far wide of the mark but the initial p
observation was valid; we now know that having children makes a woman less likely to develop breast cancer. y
p
In 1901 The Lancet observed that cervical cancer was rare amongst Jewish women. Suspecting that the disease was caused by excess salt, the writer surmised that Jews were less susceptible because they did not eat bacon. An alternative explanation was offered when the subject was revisited in 1959, with a doctor speculating that circumcision reduced the risk (1). Neither were correct i
ii
d d h i k (1) N i h
about the cause but, again, the association was real.
L
Lymphoma
h
b lt
belt
O í d E t i Barr
O vírus de Epstein
B
…o que especulamos
l
• AD sexo feminino diagnóstico de LMA com t8 21
t8;21
• Transplante alogénico de medula óssea com Transplante alogénico de medula óssea com
dador do sexo masculino
• Recaída após o transplante com a mesma translocação mas agora em células XY
translocação, mas agora em células XY
O í
Os vírus como agentes terapêuticos
t t
ê ti
• No início do século XX (finais do séc. XIX?) médico italiano reporta resposta de cancro édi it li
t
t d
colo do útero a vacina da raiva.
R
Resposta de LLA a varicella
t d LLA
i ll
• Em 1940 um adolescente, em Boston, teve uma remissão de leucemia, apos varicela.
i ã d l
i
i l
Ao fim de um mês recaída da doença
• Ao fim de um mês recaída da doença
Utili ã d í
Utilização de vírus oncolíticos
líti
• Adenovírus
• Modificações para aumentar a afinidade (usar a cromogranina como promotor)
a cromogranina
como promotor)
• Modificação para diminuir a toxicidade (miRNA)
…mas a charlatanice…
h l t i
A virus that kills cancer: the cure that's waiting in the cold
g
Sitting in a refrigerator in a Swedish laboratory is what promises to be a cheap and effective cancer treatment. So why are the trials to bring it to market not going ahead?
going ahead? On the snow‐clotted plains of central Sweden where Wotan and Thor, the clamorous gods of magic and death, once held sway, a young, self‐deprecating gene therapist has invented a virus that eliminates the type of cancer that killed Steve Jobs. Name of the Trial
Phase II Randomized Study of Seneca Valley Virus‐001 (NTX 010) ft Pl ti
(NTX‐010) after Platinum‐Based Chemotherapy in Patients B d Ch
th
i P ti t
with Extensive‐Stage Small Cell Lung Cancer (NCCTG‐
N0923)
A Phase 2b Randomized Trial of JX‐594 (Vaccinia GM‐CSF / TK‐deactivated
GM‐CSF / TK‐deactivated Virus) Plus
Virus) Plus
Best Supportive Care Versus Best Supportive
Care in Patients With Advanced Hepatocellular
C i
Carcinoma Who
Wh Have
H
F il d Sorafenib
Failed
S f ib
Treatment