MedLine Search: SMANCS
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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.
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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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