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surrounding normal tissue. Treatment groups consisted of mice with tumors
treated with medium or ALA and Oph for 3 h in darkness, followed by illumination
for 30 min.
The initial mean tumor sizes in both control and treated mice (n
3) were
similar. Mice were allocated randomly to treatment groups. Tumors that received
ALA and Oph photodynamic therapy (3 h incubation before a 30-min illumination)
were significantly reduced 5.4-fold in size compared to control tumors by day 1 and
at all subsequent time points
(P
ΒΌ
0.05). By days 4 and 5, there were no palpable
tumors in 5 of the 6 treated mice. In contrast, the control tumors doubled in size by
days 4 and 5
(P
<
<
0.05). On day 1, one of the treated mice sacrificed for histopa-
thology appeared to have a palpable tumor, but histopathological examination
showed only edema and epidermal necrosis with no evidence of sarcoma tissue
present (Rebeiz et al.
1996b
). Subsequent histopathology confirmed that in ALA
and Oph-phototreated mice, the Meth-A tumor tissue, which is non-metastasizing,
was eradicated, except for a small amount of sarcoma tissue in one mouse. In 5 of
6 mice in which the tumor tissue was eradicated, only necrotic sarcoma tissue
remained, indicating a high level of tumor necrosis. In addition, one-half of the
ALA and Oph-treated mice had panniculitis and epidermal and dermal damage.
This is consistent with a local inflammatory response occurring at the site of ALA
and Oph injection and is commonly observed in patients treated with ALA photo-
dynamic therapy (Grant et al.
1993
; Kennedy et al.
1990
; Wolf et al.
1993
). Neither
panniculitis nor tumor necrosis was evident in control mice.
Histopathological sections of control tumors and lesions 3 days after ALA and
Oph photodynamic therapy were examined. Meth-A tumors were undifferentiated,
as reported earlier (Chun and Hoffman
1987
). In control mice, there was some
necrosis of adjacent dermis related to expansion of the tumor, and the tumor showed
muscle invasion, which is typical of established tumors (Rebeiz et al.
1996b
).
Some panniculitis was apparent, along with necrosis of the epidermis and
inflammation of the dermis, sloughing of the skin, and keratinization, which are
all indicators of a photodynamic reaction occurring at the site of injection.
References
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Cohen JJ, Duke RC, Fadok VAS, Sellins KS (1992) Apoptosis and programmed cell death in
immunity. Ann Rev Immunol 10:267-293
Dailey HA (1990) Conversion of coproporphyrinogen to protoheme in higher eukaryotes and
bacteria: terminal three enzymes. In: Dailey HA (ed) Biosynthesis of heme and chlorophylls.
McGraw-Hill, New York, pp 123-161
Dive C, Hickman JA (1991) Drug-target interactions: only the first step in the commitment to a
programmed cell death. Br J Cancer 64:192-196
Dougherty TJ (1987) Photosensitizers: therapy and detection of malignant tumors. Photochem
Photobiol 45:879-889
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