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CancerGuide: Alternative and Complementary Therapies

Evaluating Alternative Therapies
Separating The Wheat From the Chaff (will open in new window!)
Promising Therapies
+ PSK
Lesser Known Therapies
SMANCS References
Popular Therapies
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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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