MedLine Search: SMANCS

Legacy MedLine Search

This MedLine Search of the technical medical literature is from the early days of CancerGuide so it may not include the latest research. The articles referenced are still relevant but more recent ones may also be available. For more information on the incredibly powerful and freely available MedLine database see my Article on MedLine.

In all cases I have selected the references that looked most interesting to me. These are searches with a point of view! There could be references on this same subject that I didn’t include that you would have. For both of these reasons as well as the age of the search, you may want to consider doing your own search on this subject after looking at mine.

Finally, keep in mind that the abstracts presented here are only summaries of the actual articles. If you want to delve deeper you may want to get some of these articles from a Medical Library or an online document delivery service, as is provided with all MedLine accesses (usually for a fairly substantial fee).

FRI APR 19,1996 7:33 PM
PaperChase provides 9,125,978 references -- all references found in the
following databases of the National Library of Medicine and the National
Cancer Institute*.  You are searching all four databases simultaneously.
Database    Indexing Began    Updated     Current through
MEDLINE        1966          weekly       May 1996 Update, Part 5
HEALTH         1975          monthly      December 1995 Update
AIDSLINE       1980          monthly      April 1996 Update
*CANCERLIT      1980          monthly      March 1996 Update
LIST                    REFERENCES   LIST                     REFERENCES
A) SMANCS                      44    E) ZINOSTATIN                  648
B) MAEDA H...                1150    F) ZINOSTATIN /MX/TU           531
C) NEOPLASMS         1176613    G) HUMAN                   5712830
D) *ON B&C;                    272    H) *ON F&G;                     241
*****CANCER RESEARCH*****
(REFERENCE 1 OF 23)
87051361
Matsumura Y  Maeda H
A new concept for macromolecular therapeutics in cancer chemotherapy:
mechanism of tumoritropic accumulation of proteins and the antitumor
agent smancs.
In: Cancer Res (1986 Dec) 46(12 Pt 1):6387-92
We previously found that a polymer conjugated to the anticancer
protein neocarzinostatin, named smancs, accumulated more in tumor
tissues than did neocarzinostatin. To determine the general mechanism
of this tumoritropic accumulation of smancs and other proteins, we
used radioactive (51Cr-labeled) proteins of various molecular sizes
(Mr 12,000 to 160,000) and other properties. In addition, we used dye-
complexed serum albumin to visualize the accumulation in tumors of
tumor-bearing mice. Many proteins progressively accumulated in the
tumor tissues of these mice, and a ratio of the protein concentration
in the tumor to that in the blood of 5 was obtained within 19 to 72
h. A large protein like immunoglobulin G required a longer time to
reach this value of 5. The protein concentration ratio in the tumor
to that in the blood of neither 1 nor 5 was achieved with
neocarzinostatin, a representative of a small protein (Mr 12,000) in
all time. We speculate that the tumoritropic accumulation of these
proteins resulted because of the hypervasculature, an enhanced
permeability to even macromolecules, and little recovery through
either blood vessels or lymphatic vessels. This accumulation of
macromolecules in the tumor was also found after i.v. injection of an
albumin-dye complex (Mr 69,000), as well as after injection into
normal and tumor tissues. The complex was retained only by tumor
tissue for prolonged periods. There was little lymphatic recovery of
macromolecules from tumor tissue. The present finding is of potential
value in macromolecular tumor therapeutics and diagnosis.
Institutional address:
Department of Microbiology
Kumamoto University Medical School
Japan.
*****ANTICANCER RESEARCH*****
(REFERENCE 2 OF 23)
90314329
Noda S  Konno S  Tanaka J  Yamada M  Yoshitake N
Treatment of renal cell carcinoma with intra-arterial administration
of SMANCS dissolved in Lipiodol.
In: Anticancer Res (1990 May-Jun) 10(3):709-15
Patients 1 with an unresectable clear-cell carcinoma of the kidney
was treated by intra-arterial administration of SMANCS dissolved in
an oily medium, Lioidol, (SMANCS/Lipiodol). It was previously shown
that targeting chemotherapy could be achieved for hepatoma by the
arterially administered SMANCS/Lipiodol. In this study,
SMANCS/Lipiodol was administered for renal cancer and the selective
remaining of SMANCS/Lipiodol in renal cancer was observed in this
patient. Patient 1, after three years and five months of repeated
arterial injection of the drug, the patient's physical condition
recovered sufficiently, reduction in tumor size was observed and the
tumor became resectable. Patient 2 with renal carcinoma (4 cm in
diameter) was treated by intra-arterial injection of SMANCS/Lipiodol
and resected for prevention of postoperative recurrence. More than
90% of the tumor showed necrosis. Definite anticancer effects of the
preoperative arterial administration of SMANCS/Lipiodol can be
observed both clinically and histologically.
Institutional address:
Department of Urology
Kurume University of Medicine
Japan.
(REFERENCE 3 OF 23)
89321376
Oda T  Sato F  Yamamoto H  Akagi M  Maeda H
Cytotoxicity of smancs in comparison with other anticancer agents
against various cells in culture.
In: Anticancer Res (1989 Mar-Apr) 9(2):261-5
The cytoxicity of neocarzinostatin (NCS) and smancs [copoly(styrene
maleic acid)-conjugated NCS] to various cultured cells was compared
with that of several other antitumor agens in clinical use on various
malignant and non-malignant cells as regards to their effect on
colony formation of cells. Both NCS and smancs showed the most potent
cytotoxicity against all tumor cell lines tested; the IC50s (colony
inhibitory concentration 50%) of these drugs were 3.2-20 nM, 10-1000
times lower than those of other drugs. In contrast, NCS and smancs
exhibited relatively lower toxicity to normal cells such as human
skin fibroblasts and chick embryonic fibroblasts (IC50, about 50 and
100 nM, respectively). Normal rat hepatocytes were found to be very
resistant to NCS and smancs (both IC50s were about 500 nM). Moreover,
the minimum exposure time of smancs to cultured tumor cells required
to achieve effective cytotoxic activity was much shorter than that of
NCS and other drugs. Namely, at 30 nM more than 80% cells were killed
by exposure to smancs for only a few minutes, whereas with NCS more
than 80 min of exposure time was required. It was also found that
smancs inhibited the uptake of 3H-thymidine into DNA as expected.
These results clearly indicate that smancs is an unique antitumor
agent with a broad antitumor spectrum which exhibits some
characteristics similar to, but also some very different from NCS.
Institutional address:
Department of Microbiology
Kumamoto University School of Medicine
Japan.
*****CANCER*****
(REFERENCE 4 OF 23)
85048558
Konno T  Maeda H  Iwai K  Maki S  Tashiro S  Uchida M  Miyauchi Y
Selective targeting of anti-cancer drug and simultaneous image
enhancement in solid tumors by arterially administered lipid contrast
medium.
In: Cancer (1984 Dec 1) 54(11):2367-74
Twenty-four patients with various solid tumors including metastatic
liver cancer and cancer of the lung, gallbladder, and pancreas were
treated with a lipophilic macromolecular drug, copoly(styrene-maleic
acid) conjugated neocarzinostatin (SMANCS). The drug was dissolved in
a lipid contrast medium Lipiodol and administered by catheterizing
the respective feeding arteries under x-ray monitoring. The
advantages of this therapy include: (1) selective deposition of
Lipiodol with the anti-cancer drug in the target tumor, (2) a
pronounced and long-lasting anti-cancer effect, (3) enhanced
visualization of the tumor on x-ray examinations for a prolonged
period which also facilitated the long-term follow-up, (4)
semiquantitative evaluation of the dosage regimen by x-ray
examination before further administration, (5) general applicability
due to procedural simplicity, and (6) little side effect. Since the
amount of Lipiodol and SMANCS used per administration for a patient
(1.0-5.0 ml; 1.0-5.0 mg) was far less than the anticipated toxicity
(LD50 of Lipiodol = 95 ml/60 kg, dog, intravenously; and that of
SMANCS = 3.4 mg/kg, mouse, IV), no deleterious effects to such
critical organs as the brain, heart, lung, liver, or kidneys were
observed upon radiologic and general clinical examination.
Institutional address:
Department of Surgery
Kumamoto University Medical School
Japan.
(REFERENCE 5 OF 23)
87159165
Ohtsuka N  Konno T  Miyauchi Y  Maeda H
Anticancer effects of arterial administration of the anticancer agent
SMANCS with lipiodol on metastatic lymph nodes.
In: Cancer (1987 May 1) 59(9):1560-5
A new method of arterially administering an oily anticancer agent was
successfully established for the selective targeting of metastatic
lymph nodes. A high molecular weight anticancer agent, a conjugate of
copolymer (styrene maleic acid) to neocarzinostatin (SMANCS) was
prepared in our laboratory and dissolved in a lymphographic oily
contrast medium, Lipiodol (SMANCS/Lipiodol). SMANCS/Lipiodol was
administered intraoperatively to eight patients with colorectal
cancer and preoperatively to one patient with gastric cancer with
lymph node metastases. In six of the patients with colorectal cancer,
the drug was administered via an artery and in the other two patients
the drug was injected into the wall of the colon near the primary
cancer. In the patient with gastric cancer, the drug was administered
via the left gastric artery. Delivery of the drug to the lymph nodes
was examined roentgenologically and the anticancer effect was
examined histologically. The results showed that SMANCS/Lipiodol
could be delivered to the metastatic lymph node via the artery, but
it could not be delivered to the metastatic lesion of the lymph node
via the lymphatic route. In the patient with gastric cancer,
SMANCS/Lipiodol preoperatively administered via an artery was found
to remain selectively in a metastatic lymph node and an anticancer
effect was histologically proved in all three of the metastatic lymph
nodes.
Institutional address:
First Department of Surgery
Kumamoto University Medical School
Japan.
*****EUROPEAN JOURNAL OF CANCER AND CLINICAL ONCOLOGY*****
(REFERENCE 6 OF 23)
84004535
Konno T  Maeda H  Iwai K  Tashiro S  Maki S  Morinaga T  Mochinaga M
Hiraoka T  Yokoyama I
Effect of arterial administration of high-molecular-weight anticancer
agent SMANCS with lipid lymphographic agent on hepatoma: a
preliminary report.
In: Eur J Cancer Clin Oncol (1983 Aug) 19(8):1053-65
A clinical evaluation of arterial infusion of high-molecular-weight
antitumor agent SMANCS dissolved in lipid lymphographic agent
(thiodol) in 44 patients with mostly unresectable hepatoma is
described. The treatment regimen demonstrated significant merits both
therapeutically and diagnostically. Marked antitumor effects were
shown in the decreased serum alpha-fetoprotein levels (86% of cases)
and tumor size (95% of cases), and in survival period and
histological findings. Furthermore, there was increased diagnostic
sensitivity using CT scan, plain X-rays or ultrasound. The procedure
of selective arterial administration of 3-4 mg of SMANCS in 3-4 ml of
ethiodol per dose was simple to perform and was required only once
every 3-4 weeks. Both ethiodol and the drug accumulated more
selectively in tumor than in any other tissues and their activity
remained for more than 3 weeks. Only minimal side-effects were
associated with SMANCS and ethiodol during this study.
Institutional address:
Department of Surgery
Kumamoto University Medical School
Japan.
*****GAN NO RINSHO. JAPANESE JOURNAL OF CANCER CLINICS*****
(REFERENCE 7 OF 23)
84292827
Tokuyama K  Jinno K  Yumoto Y  Takasima S  Fukuda K  Moriwaki S
Maeda H  Shimamura Y
[Combined treatment with intra-arterial administration of oily anti-
cancer agents and transcatheter arterial embolization--clinical and
pathological study on 2 cases with resected small hepatoma]
In: Gan No Rinsho (1984 Jul) 30(8):955-64  (Published in Japanese)
Combined treatment with intraarterial administration of oily anti-
cancer agent (SMANCS-Lipiodol; copolymer of styrene maleic acid
conjugate of Neocarcinostatin disolved in Ethiodol) and transcatheter
arterial embolization (TAE) was employed in 2 patients with small
hepatoma. At 3-4 weeks after treatment, hepatic resection was
performed. Histopathological examination of the 2 resected specimens
showed total cell necrosis; CT and Softex revealed the distribution
of lipiodol in the tumor and adjacent regions. This combination
treatment showed combined effects, i.e. embolization by TAE, the anti-
cancer effect of SMANCS and the selective delivery of lipidol to the
hepatoma, especially the area of capsula invasion, the daughter
nodule and tumor thrombus.
Institutional address:
Dept. of Internal Medicine
Shikoku Cancer Center Hospital.
*****GAN TO KAGAKU RYOHO [JAPANESE JOURNAL OF CANCER AND CHEMOTHERAPY]*****
(REFERENCE 8 OF 23)
83281653
Konno T  Tashiro S  Maeda H  Iwai K  Ogata K  Mochinaga M  Uemura K
Ishimaru S  Miyauchi Y  Yokoyama I
[Intra-arterial injection of an oily antineoplastic agent in hepatic
cancer]
In: Gan To Kagaku Ryoho (1983 Feb) 10(2 Pt 2):351-7
(Published in Japanese)
A lymphographic agent, Ethiodol, injected via the hepatic artery was
found to remain selectively in the tumor vessels of hepatoma for a
long time in our clinic. Taking advantage of this selective
continuous peripheral embolization, a lipophilic high molecular
anticancer agent, SMANCS (Copolymer of styrene maleic acid conjugated
to Neocarzinostatin) dissolved in Ethiodol was administered via the
celiac axis or the hepatic artery with Seldinger's method. Anticancer
effect was examined by histological findings of specimens removed
using hepatic resection (13 cases) and autopsy (1 case) in 14
patients receiving this treatment. Anticancer effect of this
treatment became clear through histological findings. In the patients
administered SMANCS more than 0.26 mg per 1 cm2 of maximum cut-
surface area, complete or widespread necrosis of the tumor occurred,
whereas non-cancerous liver tissue remained unaffected.
Institutional address:
Dept. of Surgery
Kumamoto University Medical School.
(REFERENCE 9 OF 23)
90025147
Maeda H
[Principle and therapeutic effect of lipophilic anticancer agent
[SMANCS/lipiodol]: selective targeting with oily contrast medium]
In: Gan To Kagaku Ryoho (1989 Oct) 16(10):3323-31
(Published in Japanese)
Lipiodol, an oily contrast medium, is utilized to deliver the
anticancer agent SMANCS to the target tumor in which the tumor
selective delivery of 2,500 fold more than plasma was confirmed with
prolonged retention in the tumor tissue. This unique tumor targeting
is accomplished by the arterial injection of the oily formulation of
the drug. The method utilizes unique vascular properties of tumor
tissue. SMANCS is a derivative of neocarzinostatin conjugated with
copolymer of styrene and maleic acid. It has much propronounced
lipophilicity, stability against various harsh environments and
exerts a potent cytotoxicity. Therapeutic effect of the drug to
unresectable primary hepatoma is much better than the conventional
method. For Child A category patients with intrahepatic metastasis in
no more than three area, a 3 yr survival rate is more than 87%. When
the Child's A and B are combined with no distant metastasis, 1-, 2-
and 3-year survival rates are 87%, 50%, and 35%, respectively. The
side effect of this treatment [SMANCS/Lipiodol, i.p.] is minimal;
transitory low grade fever is the commonest one (40-50% of cases)
which can be controlled by a routine protocol. No liver or marrow
toxicity was observed. Procedural limitations for the lung cancer
etc. are discussed.
Institutional address:
Dept. of Microbiology
Kumamoto University
Medical School.
(REFERENCE 10 OF 23)
89391490
Kubo M  Fuchigami T  Murata S  Konno T  Maeda H
[A case of massive hepatoma which responded to SMANCS/Lipiodol
regimen with intra-arterial infusion]
In: Gan To Kagaku Ryoho (1989 Aug) 16(8 Pt 2):2953-6
(Published in Japanese)
Transcatheter arterial chemotherapy (SMANCS/lipiodol) was applied to
massive hepatoma, which had a high AFP 213,000 ng/ml, A-P shunt,
tumor thrombosis and metastatic lung cancer. After 3 months, the AFP
value reduced to 18 ng/ml, massive hepatoma and the A-P shunt
disappeared, but AFP-negative nodular hepatoma recurred around
initial hepatoma. Each time, we injected SMANCS/lipiodol to the
recurring hepatoma. The therapy in the initial stage was not so
effective. The portal vein was not observed in the initial stage, but
appeared after the second dosage. Metastatic lung cancer was
declining in the initial dosage and 23 months later disappeared after
the third dosage. The massive hepatoma occupied entirely the rt. lobe
of the liver. The patient lived for 4 years, had total admission
periods of 190 days and could return to life in society. In this
case, we considered that transcatheter arterial chemotherapy
(SMANCS/lipiodol) had remarkable effects.
Institutional address:
Dept. of Gastroenterology
Matsuyama Red Cross Hospital.
(REFERENCE 11 OF 23)
88268090
Konno T  Maeda H
[Targeting cancer chemotherapy using lipiodol as a carrier of
anticancer drugs for hepatocellular carcinoma]
In: Gan To Kagaku Ryoho (1988 Apr) 15(4 Pt 2-1):1043-50
(Published in Japanese)
We have found that the lipid lymphographic agent, Lipiodol
ultrafluid, remains selectively in hepatocellular carcinoma and other
malignant solid tumors. Lipiodol administered arterially flows into
the normal blood vessels of normal tissues and into the
neovasculature of the tumor. Selective retention of Lipiodol in the
tumor occurs due to early removal from the normal blood vessels and
retention in the neovasculature and extravascular space in the tumor.
Using this characteristic nature of Lipiodol, targeting cancer
chemotherapy was achieved. It was shown that anticancer drugs had to
be dissolved in Lipiodol and diffuse out gradually from the agent in
order to achieve targeting cancer chemotherapy. Various kinds of oily
anticancer agents which facilitate targeting cancer chemotherapy,
such as SMANCS/Lipiodol, mitomycin/Lipiodol, adriamycin/Lipiodol and
aclarubicin/Lipiodol were successfully developed. Clinically, these
oily anticancer agents were administered to 260 patients with
hepatocellular carcinoma. Selective long-lasting retention of
Lipiodol in hepatocellular carcinoma was proved on the basis of CT
and low-kVp X-ray examination, and persistent high biological
activities of anticancer drugs in the tumor were also recognized. The
serum AFP level and tumor size showed a decrease in 92% and 90% of
cases, respectively. The survival period of these patients with
unresectable tumor treated with this protocol was definitely longer
than in the comparison group, i.e., the 50% survival period for the
comparison group was 1.3 months, while that of the patients who
received this protocol was 13 months. In patients administered a
SMANCS dose of more than 0.25mg/cm2 of maximum cut-surface area,
complete necrosis of the tumor was found, and importantly, non-
cancerous liver tissue remained unaffected. Neither hematosuppression
nor any severe side effects due to anticancer drugs were observed.
Remarkable antitumor effects and reduced side effects could thus be
achieved by targeting chemotherapy using Lipiodol as a carrier of
anticancer drugs.
Institutional address:
1st Dept. of Surgery
Kumamoto University Medical School.
(REFERENCE 12 OF 23)
95398465
Hirashima N  Kumada K  Sakakibara K  Hirai T  Nemoto S  Matsuura H
Itazu I  Nojiri O  Kano H
[Combination of transcatheter arterial infusion of SMANCS and
embolization on hepatocellular carcinoma]
In: Gan To Kagaku Ryoho (1995 Sep) 22(10):1411-5  (Published in Japanese)
[No Abstract Available]
Institutional address:
Dept. of Gastroenterology
Chukyo Hospital Nagoya.
(REFERENCE 13 OF 23)
96144763
Inoue Y  Nakamura H
[Two cases of long-term survival with hepatocellular carcinoma
following targeting therapy with SMANCS/lipiodol]
In: Gan To Kagaku Ryoho (1996 Jan) 23(1):99-101  (Published in Japanese)
We performed arterial infusion of SMANCS/Lipiodol in nineteen cases
with hepatocellular carcinoma (HCC). We report two of these cases who
survived for more than five years after the initial treatment. In
case 1, HCC responded very well to the initial subsegmental infusion
of SMANCS/Lipiodol with a prominent decrease in AFP level. In case 2,
a 63-year-old male, repeated subsegmental infusion of SMANCS/Lipiodol
for the local recurrence controlled the tumor well. In both cases, an
approximately three-year period of complete remission passed until
the tumor recurred. Arterial infusion of SMANCS/Lipiodol is expected
to be a potent treatment for HCC. Its administration should be
subsegmental, if possible, and should be repeated for local
recurrence with a careful follow-up study.
Institutional address:
Dept. of Radiology
Minoo City Hospital.
(REFERENCE 14 OF 23)
86267842
Konno T  Ohtsuka N  Yamasaki K  Mizutani J  Miyauchi Y  Maeda H
Matsumura Y
[Targeting of anticancer chemotherapy utilizing the characteristic
nature of the neovasculature of solid tumors]
In: Gan To Kagaku Ryoho (1986 Apr) 13(4 Pt 2):1448-55
(Published in Japanese)
We have been able to achieve targeting of anticancer treatments using
the differences between the neovasculature of solid tumors and the
vasculature of normal tissues. The first of these differences was as
follows; We discovered that when the lipid contrast medium, Lipiodol,
was administered arterially, it remained selectively in the solid
tumor for a long time. Using this characteristic nature of Lipiodol,
we achieved targeting of anticancer chemotherapy by arterial
administration of oily anticancer drugs solubilized in Lipiodol.
Remarkable anticancer effects against various malignant solid tumors
were observed using this targeting chemotherapy. The second of the
above differences, studied by Suzuki, is responsiveness to
angiotensin II, in which the blood flow in the tumor can be increased
using this vasoconstrictor. With Angiotensin II, a larger volume of
oily anticancer drugs could be delivered to the tumor. The third
difference is the permeability of the neovasculature to drugs of high
molecular weight and the duration that these drugs remain in the
extracapillary space. The high-molecular-weight anticancer agent,
SMANCS (m.w. 17,000) dissolved in 5% glucose solution, was
administered intravenously, and its histological antitumor effects on
gastric cancer and esophageal cancer were clearly observed.
Institutional address:
First Dept. of Surgery
Kumamoto University Medical School.
(REFERENCE 15 OF 23)
85173380
Maeda H  Konno T
[Tumor-targeted chemotherapy with lipid contrast medium and macro
molecular anticancer agents theoretical considerations and clinical
outcome]
In: Gan To Kagaku Ryoho (1985 Mar) 12(3 Pt 2):773-82
(Published in Japanese)
Theoretical considerations for tumor-selective chemotherapy are
described which based on the unique character of the tumor
neovasculature. Namely, most solid tumors possess four different
unique features: hypervasculature, enhanced permeability even to
macromolecules, architectural differences, and lack of the lymphatic
recovery system. Lipid or lipid contrast medium and macromolecular
anticancer agents using prototype drug smancs can be utilized for
cancer-selective targeting based on the above four features.
Selective targeting with lipid contrast medium with smancs has
offered two clinical benefits; definite and pronounced antitumor
effect and diagnostic value. These effects can be primarily
attributed to the tumor-selective accumulation of the agent, i.e.,
more than 1,000 times greater in the tumor than in the plasma. As a
onsequence very few side effects are observed clinically. Primary or
secondary hepatoma and lung cancer showed size reduction in more than
90 % of treated patients. Very few side effects such as
hematosuppression or inhibited liver function were observed in these
cases. Prolongation of life-span was marked in the patients. The
above results indicate a new future direction for the development of
the tumor-selective chemotherapy.
Institutional address:
Dept. of Microbiology
Kumamoto University Medical School.
(REFERENCE 16 OF 23)
94241743
Maeda H
[SMANCS/lipiodol]
In: Gan To Kagaku Ryoho (1994 May) 21(6):907-13  (Published in Japanese)
SMANCS is the first commercially available polymer conjugated drug
invented by the author, in which the protein antitumor agent
neocarzinostatin is conjugated with two short chains of poly(styrene-
comaleic acid) half-butylate. It exhibits the highest tumor/blood
ratio (> 1,000) when injected arterially as an oily formulation in
Lipiodol (SMANCS/Lipiodol). In addition, SMANCS/Lipiodol can give
very high tumor contrasting image under X-ray (e.g., CT-scan), and
thus the optimal dosing regimen can be determined and offers a
diagnostic advantage. Phase I/II study of SMANCS was initiated in
1989 and it was approved by the Japanese Government in the fall of
1993 for the treatment of hepatoma. Exploitation of its application
for other tumors such as renal cell cancer and pleural/ascitic
carcinomatosis is anticipated. The response rate of Grad IV Lipiodol
retention is 48.5% at 4 months; and those of 6 and 12 months are 50%
and 90%, respectively. The major side effect is fever, which is only
transitory, and no bone-marrow suppression, renal or hepatic toxicity
were observed.
Institutional address:
Dept. of Microbiology
Kumamoto University School of Medicine.
(REFERENCE 17 OF 23)
83255088
Matsukado Y  Maeda H  Uemura S  Kuratsu J  Sonoda H
[Pharmacokinetic one-compartment model using neocarzinostain as a
prototype drug and its clinical application to chemotherapy for brain
tumor. Part II. A clinical trial with selected protocol]
In: Gan To Kagaku Ryoho (1982 Nov) 9(11):1933-41  (Published in Japanese)
Neocarzinostatin as previously reported, appeared to exhibit an
intense cytotoxicity to the glioblastoma cells and some other
malignant brain tumor cells, such as pineal germinoma or
medulloblastoma, which are notoriously known to disseminate into the
cerebrospinal fluid space. In vitro study, the minimum susceptibility
of glioblastoma cells to neocarzinostatin was found to be below 0.005
microgram/ml, whereas normal glia cells were not affected at 0.3
microgram/ml. This study indicated that neocarzinostatin was
extremely effective in the treatment of malignant brain tumor without
affecting normal neural tissue. Pharmacokinetic study was performed
in order to establish intermittent intrathecal perfusion therapy and
to prevent subarachnoid dissemination of the brain tumor cells.
Experimental results were applied to the treatment of 12 patients
with brain tumor, who had shown positive cytology of the
cerebrospinal fluid. Follow-up investigation showed quite a favorable
result and it was considered that prophylactic irradiation to the
entire spinal column could be replaced with intrathecal
administration of neocarzinostatin. During clinical application no
noticeable side effect was encountered and active stimulation of
macrophages, which were mobilized into the CSF space, was another
unexpected advantage of this treatment.
Institutional address:
Dept. of Neurosurgery
Kumamoto University Medical School.
(REFERENCE 18 OF 23)
83255097
Konno T  Maeda H  Yokoyama I  Iwai K  Ogata K  Tashiro S  Uemura K
Mochinaga M  Watanabe E  Nakakuma K  Morinaga T  Miyauchi Y
[Use of a lipid lymphographic agent, lipiodol, as a carrier of high
molecular weight antitumor agent, smancs, for hepatocellular
arcinoma]
In: Gan To Kagaku Ryoho (1982 Nov) 9(11):2005-15  (Published in Japanese)
Two advantages of the present therapeutic approach were described.
Firstly, a selective deposition of lipiodol in tumor tissue was
verified, thus more precise and accurate diagnosis by X-rays was
possible either by CT or plain X-ray film. Secondly, pronounced
accumulation of smancs in tumor tissue was observed, which
established highly effective chemotherapy of unresectable hepatoma of
22 cases and 12 other cases based on (a) decrease in alpha-
fetoprotein (86%), (b) tumor size (95%) and histology. Drug was given
via the hepatic artery mostly 3-4 mg in 3-4 ml of lipiodol once every
3 to 4 weeks. Most patients have experienced a total dose of 6-8 mg
in two cycles, but drug activity lasted more than 3 weeks. Neither
hematosuppression nor anaphylaxis was observed. Major side effect was
transient fever (38-39 degrees C) in about 50% of the cases which
lasted no more than one week. Other minor side effect was abdominal
pain during or after arterial infusion which lasted for about 20 min.
Liver function was affected very slightly if any. Mild leukocytosis
was observed in 65% of the patients.
Institutional address:
First Dept. of Surgery
Kumamoto University Medical School.
*****INTERNATIONAL JOURNAL OF HYPERTHERMIA*****
(REFERENCE 19 OF 23)
91268649
Yumoto Y  Jinno K  Tokuyama K  Wada T  Kobashi H  Okamoto T  Toki H
Inatsuki S  Hara K  Moriwaki S  et al
Trans-catheter hepatic arterial injection of lipiodol soluble anti-
cancer agent SMANCS and ADR suspension in lipiodol combined with
arterial embolization and local hyperthermia for treatment of
hepatocellular carcinoma.
In: Int J Hyperthermia (1991 Jan-Feb) 7(1):7-17
The clinical effect and safety of Lp-TAE alone and combined with
radiofrequency (RF) capacitive hyperthermia (HT) were evaluated in 20
patients with hepatocellular carcinoma (HCC) associated with
cirrhosis of the liver. After the oily carcinostatic agents were
administered by Lp-TAE, HT, at a temperature of greater than 42.5
degrees C, was induced for 40 min, twice a week by an RF of 8 MHz for
a total of 10 to 38 times. The response rate was 40% in the 10 cases
that were treated with Lp-TAE combined with HT and 20% in the 10
cases that were treated with Lp-TAE. The patients who were treated
with Lp-TAE combined with HT had a tendency to have better survival
rates than those of the Lp-TAE group (p less than 0.099). The main
side-effects of Lp-TAE combined with HT were low-grade fever,
localized pain, myelo-suppression and liver dysfunction, but these
were transient and eventually disappeared.
Institutional address:
Radioisotope Center
Okayama University
Japan.
*****JAPANESE JOURNAL OF MEDICINE*****
(REFERENCE 20 OF 23)
85211615
Tashiro S  Maeda H
Clinical evaluation of arterial administration of SMANCS in oily
contrast medium for liver cancer.
In: Jpn J Med (1985 Feb) 24(1):79-80
[No Abstract Available]
Institutional address:
First Department of Surgery
Kumamoto University Medical School.
*****Monograph*****
(REFERENCE 21 OF 23)
89649323
Konno T  Maeda H
TARGETING CHEMOTHERAPY OF HEPATOCELLULAR CARCINOMA: ARTERIAL
ADMINISTRATION OF SMANCS/LIPIODOL
In: Neoplasms of the Liver. Okuda K, Ishak KG, eds. New York, Springer,
1987. (1987):343-52
Targeting chemotherapy of hepatocellular carcinoma (HCC) is performed
by arterial administration of anticancer agents, such as styrene
maleic acid conjugates of neocarzinostatin (SMANCS), mitomycin C
(MMC), or aclarubicin (ACR) dissolved in Lipiodol (LPD). As
SMANCS/LPD, MMC/LPD, ACR/LPD, or a mixture of them, these oily
anticancer agents were administered by catheterization of the celiac
or hepatic artery under x-ray monitoring. Anticancer effect and the
advantages of this targeting chemotherapy for HCC are described,
including the principle of tumor targeting by LPD, drug preparation,
patients (pts) and procedures, differentiation of HCC from metastatic
liver cancer, dose determination, and side effects. A total of 371
injections of SMANCS/LPD were given to 175 pts with HCC, diagnosed
either histologically or clinically; 145 pts had unresectable
advanced HCC, 30 pts had resectable tumors. Of these pts, 163 had
liver cirrhosis. There were 13 pts with HCC Stage 1, 35 pts Stage 2,
27 pts Stage 3, and 60 pts Stage 4, according to Japanese Society for
Cancer Treatment criteria. An av of 4 mg SMANCS/LPD per injection was
given by arterial infusion through the celiac (71x), common hepatic
(170x), proper hepatic (79x), or other peripheral arteries (51x). The
serum alpha-fetoprotein level and tumor size decreased in 91% of pts
with resectable HCC and 93% of the pts with unresectable HCC. In 98
tumors, 41 showed more than 50% reduction in size within 1-12 months.
The major side effect observed was fever of 38-39 C (52% of pts).
Most pts became afebrile in a few days. About 14% of the pts
experienced dull pain in the upper abdomen which lasted for about 15
min after the infusion. Mild and transitory elevation of SGOT and
SGPT occurred in 23% and 13% of pts, respectively. Unexpectedly,
moderate leukocytosis occurred in 45% of pts after infusion. Arterial
administration of oily anticancer agents to pts with HCC had the
following advantages: (1) the anticancer effect is definitive in the
majority of cases; (2) side effects due to anticancer agents appear
to be minimal; (3) LPD is useful as an imaging agent which provides
high contrast on computed tomography and assists in the follow-up
study of pts; (4) superselective catheterization is not always
necessary, thereby making the procedure practical in most hospitals;
(5) in many cases, pts can be discharged 1 wk after arterial
administration of the drugs and can be followed-up as outpatients;
and (6) the procedure is safe. (12 Refs)
Institutional address:
First Dept. of Surgery
Kumamoto Univ. Medical Sch.
Honjo
Kumamoto
860 Japan
*****NIPPON GEKA GAKKAI ZASSHI.  JOURNAL OF JAPAN SURGICAL SOCIETY*****
(REFERENCE 22 OF 23)
85061055
Konno T  Iwai K  Maki S  Tashiro S  Miyauchi Y  Maeda H  Yokoyama I
[Arterial administration of SMANCS and other antitumor agents
dissolved in lipiodol for various malignant solid tumors]
In: Nippon Geka Gakkai Zasshi (1984 Sep) 85(9):1151-6
(Published in Japanese)
Selective deposition of lipiodol in primary and metastatic liver
cancer, lung cancer, gallbladder cancer, pancreatic cancer and renal
cancer was elucidated by plain X-ray film and CT. Selective delivery
of anticancer agent, SMANCS was also proved by measurement of its
biological activities of removed specimen. Because of these selective
delivery of anticancer agent and embolization of neovasculature in
the tumor, highly effective chemotherapy of unresectable cancer was
established. Drug was given via celiac, the hepatic, bronchial or
renal artery mostly 1-5 mg in 1-5 ml of lipiodol once every 3-8
weeks. Antitumor effects of this therapy for hepatocellular carcinoma
was confirmed based on decrease in AFP levels (92% of the cases),
reduction in tumor size (90% of the cases) and histology. In 76
percent of the patients with the other malignant solid tumors
reduction in tumor size was recognized. Decrease in CEA level
occurred in 88 percent of the cases with metastatic liver cancer and
lung cancer. Major side effect was transient fever in about 50% of
cases. Mitomycin C and aclarubicin dissolved in lipiodol showed
remarkable antitumor effects for experimental liver cancer.
Institutional address:
First Dept of Surgery
Kumamoto University Medical School
Japan.
*****UROLOGY*****
(REFERENCE 23 OF 23)
91157356
Kobayashi M  Imai K  Sugihara S  Maeda H  Konno T  Yamanaka H
Tumor-targeted chemotherapy with lipid contrastmedium and
macromolecular anticancer drug (SMANCS) for renal cell carcinoma.
In: Urology (1991 Mar) 37(3):288-94
Twenty-five patients with renal cell carcinoma were treated with a
lipophilic macromolecular drug, poly(stylene-co-maleic acid)-
conjugated neocarzinostatin (SMANCS) dissolved in lipid contrast
medium (Lipiodol). The drug was injected by catheterizing the renal
artery and another feeding artery in 24 patients, and in the common
hepatic artery in 1 patient with metastases to the liver after a
radical nephrectomy. The procedure of selective arterial
administration of 3-20 mg/mL of SMANCS/Lipiodol was simple to perform
and was required once every two to three weeks. Total dose of SMANCS
for each patient varied from 3 to 57 mg. Both SMANCS and Lipiodol
accumulated more selectively in tumor than in any other tissue and
remained in the neovasculature and extracapillary space for a long
time. CT pattern of the remaining oil contrast medium in the tumor
was characterized by the high-density area localized mainly in the
periphery of the tumor around the central necrosis. When
hyperviscosity Lipiodol (Lipiodol HV) was used as lipid contrast
medium, it remained more persistently in the tumor and disappeared
more slowly than Lipiodol. Moreover, the pronounced anticancer effect
was recognized when SMANCS/Lipiodol HV was administered compared with
only SMANCS/Lipiodol. Severe side effects, such as myelosuppression,
unendurable pain, paralytic ileus, etc., were not observed. This
targeting chemotherapy may be of great significance for advanced
renal cell carcinoma.
Institutional address:
Department of Urology
Gunma University School of Medicine
Japan.

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