A randomized trial comparing ftorafur alone with ftorafur plus tamoxifen in postoperative adjuvant therapy for breast cancer. Kinki Area Research Group for Postoperative Adjuvant Therapy for Breast Cancer.

A randomized study was performed in 35 centers in the Kinki area of Japan to determine the effectiveness of ftrorafur (FT) plus tamoxifen (TAM) compared with FT monotherapy in postoperative adjuvant therapy for breast cancer. Patients were randomized by the envelope method to receive either FT 600 mg/day or FT 600 mg/day plus TAM 20 mg/day orally for 1 year, starting on day 7 after mastectomy. Between April 1982 and January 1985, 628 patients were assigned to treatment with FT alone and 626 to treatment with FT + TAM. Of these, 571 (90.9%) and 539 (86.1%) patients, respectively, met the eligibility requirements for this study. There were no significant differences in major background factors between the two groups of eligible patients. Five-year survival rates were 91.4% for FT alone and 91.1% for FT+TAM (not significantly different). Five-year disease-free survival rates showed a tendency towards a better prognosis (P = 0.090) in the FT + TAM group, with observed rates of 83.0% for FT alone and 86.7% for FT + TAM. Stratified analysis showed that disease-free survival with FT + TAM is better than with FT alone for patients aged 50 years or more ( P = 0.048) and for patients with from one to three positive nodes (P = 0.064).

[Quality of life in patients with advanced gastric cancer receiving AO-90, a methionine-free intravenous amino acid solution, with 5-fluorouracil and mitomycin C].

We conducted a randomized, multicenter, controlled trial of AO-90, a methionine-free 7.43% intravenous amino acid solution, in patients with advanced recurrent gastric cancer. The regimen used in the study was comprised of two-week treatment cycles, with a withdrawal period between cycles. During treatment, patients were given either AO-90 (500-750 ml/day; AO/MF group) or a commercial amino acid solution (600-800 ml/day; C/MF group) by total parenteral nutrition (TPN) for 14 days concomitantly with MF therapy (5-fluorouracil 350 mg/m2/day, iv continuously for 14 days and mitomycin C 7 mg/m2, iv push on days 7 and 14). We interviewed 118 eligible and evaluable patients (72 men and 46 women; 59 cases in the AO/MF group and 59 in the C/MF group) about their quality of life immediately before the start of treatment, one week and two weeks after the start of treatment, and one week and two weeks after treatment. A 11-item questionnaire was used to interview the subjects: nine questions using a five-point scale, one question using a 100-mm linear visual analog scale, and one question using a five-grade face scale. Changes in the grades compared with baseline data were scored as 1 point (improvement of one grade or more, or 20 mm or more), 0 points (no changes), and-1 point (decline of one grade or more, or 20 mm or more). Before analyzing the significance, quality of life score data were adjusted by the Mantel-Haenszel method due to uneven distribution of subjects concerning baseline performance status and complications. Among the items questioned, subjects receiving AO-90 showed significantly higher scores in appetite, nausea, and ambulation at some evaluation time points than those receiving a methionine-containing TPN. The results show that AO-90 improved the quality of life of patients with advanced recurrent gastric cancer.

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (surgery group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the surgery departments of 53 institutions between July 1991 and March 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 138 subjects enrolled, 129 (93.5%) were eligible and 119 (86.2%) completed the scheduled treatment (AO/MF group: 57, C/MF group: 62). The overall clinical response rates in the completed cases were 26.3% (15/57) in the AO/MF group and 8.1% (5/62) in the C/MF group, and the difference between the groups was significant (p = 0.015). In particular, the response rate in the postoperative recurrent patients with measurable lesions was 42.9% (12/28) in the AO/MF group versus 12.0% (3/25) in the C/MF group (p = 0.016). Further, in the patients who were previously treated with fluoropyrimidine drugs, 29.0% (9/31) responded to the AO/MF therapy versus 8.6% (3/35) in the C/MF group (p = 0.053). The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count and hemoglobin level, nausea/vomiting and stomatitis. The differences in the incidence were not significant between the groups. Based on these results, AO-90 in the MF regimen appears to be effective in the treatment of patients with advanced gastric cancer by significantly potentiating the effects of 5-FU.

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (internal medicine group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the internal medicine departments of 24 institutions between July 1991 and May 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 53 subjects enrolled, 52 (98.1%) were eligible and 47 (88.7%) completed the scheduled treatment (AO/MF group: 23, C/MF group: 24). Although there were significant differences for age and sex between the groups, the Mantel-Haenszel test showed that these unevenly distributed characteristics did not affect the study results. The overall clinical response rates in the completed cases were 30.4% (7/23) in the AO/MF group and 16.7% (4/24) in the C/MF group. In particular, the response rate in the inoperable advanced cases with liver metastases, ascites or distant metastases was 45.5% (5/11) in the AO/MF group versus 16.7% (2/12) in the C/MF group. The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count, hemoglobin level and platelet count, nausea/vomiting, diarrhea, stomatitis, and fever. The differences in the incidence were not significant between the groups. These results show that AO-90 in combination with MF therapy is efficacious in the treatment of patients with gastric cancer.

Effect of 5-fluorouracil and UFT on experimental liver metastasis model of colorectal cancer using mouse colon 26 cells.

Effects of 5-fluorouracil (5-FU) and UFT on an experimental liver metastasis model were compared at equi-effective dosage levels against subcutaneous tumor of mouse colon 26. 5-FU at the dosage level of 40 mg/kg suppressed the subcutaneous tumor growth by 70.0% and 45.0% on day 13 and day 18, respectively, and UFT at 20 mg/kg provided almost equal suppression (63.0% and 48.0%). In the liver metastasis model, 5-FU at 40 mg/kg showed more potent prevention of the formation of metastatic foci (94.9%) than did UFT (60.4%) at 20 mg/kg. 5-FU at 40 mg/kg produced a much higher peak serum level of 5-FU than did UFT at 20 mg/kg and also showed a much higher AUC (area under the curve) level in the portal blood. These results suggest that oral administration of 5-FU might be useful in prevention of liver metastasis of colorectal cancer.

Effects of tamoxifen and the derivative (TAT) on cell cycle of MCF-7 in vitro.

The growth inhibitory activity and influences on cell-cycle progression of tamoxifen (TAM) and its derivatives [toremifene(NK), droloxifene (FK) and TAT-59 (TAT) against MCF-7, cells, an estrogen respondent human breast cancer cell line were investigated. TAM and its derivatives exhibited a dose-dependent growth inhibitory activity against MCF-7 cells in the order of TAT > FK > TAM > NK at 48 and 120 hours in vitro. 10(-6) M TAT reduced growth of MCF-7 to 25% of that of control after 120 hours incubation in the presence of 10(-8) M estradiol; however, in the case of TAM the growth of MCF-7 was 73%. FACS analysis showed that 82.7% of the cells were accumulated at G0/1 phase after 120 hours incubation with TAT and its accumulative activity was higher than that of TAM. Moreover, when TAT was used in combination with 5-FU, the accumulative effect was significantly increased. Thus it is suggested that TAT or TAT in combination with 5-FU may be a useful adjuvant treatment against breast cancer.

Homotypic and heterotypic Ca(++)-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface.

Homotypic and heterotypic cell adhesion activities of a carcinoembryonic antigen (CEA) family member, biliary glycoprotein a (BGPa), have been examined. CHO cells transfected with the cDNA for BGPa, CEA, non-specific cross-reacting antigen (NCA) and CGM6 have been used. The BGPa producers showed both homotypic and heterotypic adhesion to CEA and NCA producers. However, they hardly adhered to CGM6 producers. Calcium ion was not required for BGPa-mediated homotypic and heterotypic cell adhesion as well as for the adhesions of other members of CEA family. The results strongly suggested that BGPa may play some important roles through Ca(++)-independent cell adhesion activities.

Immunoreactivity of recombinant carcinoembryonic antigen proteins expressed in Escherichia coli.

Immunoreactivities of recombinant carcinoembryonic antigen (CEA) proteins expressed in Escherichia coli (E. coli) were analyzed in relation to the CEA domain structure [domains N, I (A1-B1), II (A2-B2), III (A3-B3) and M]. We reconstructed in a prokaryotic expression vector, pUCPL-cI, the cDNAs fro CEA-N, CEA-I, CEA-II, and CEA-III-M. The latter three were expressed as fusion products with bacterial beta-galactosidase. The recombinant proteins were solubilized by sonication in 1% sodium dodecyl sulfate (SDS) and purified by preparative SDS-polyacrylamide gel electrophoresis followed by electroelution. Their molecular weights judged from Western blotting coincided with those calculated from their cDNA sequences, respectively. By solid-phase enzyme immunoassays, the immunoreactivities of the purified recombinant proteins were tested with 21 distinct anti-CEA monoclonal antibodies (MAbs) which had been found to recognize the peptide epitopes of the CEA molecule and to be reactive with the recombinant CEA proteins expressed in Chinese hamster ovary (CHO) cells. Fourteen of the 21 MAbs reacted with the recombinant CEA proteins expressed in E. coli and confirmed the localization of the epitopes identified by using the recombinant CEA proteins expressed in CHO cells. The reactivities of 5 MAbs with the recombinant proteins expressed in E. coli were remarkably low when compared with those of the proteins expressed in CHO cells but also confirmed the localization of the epitopes identified with the recombinant CEA proteins expressed in CHO cells. The remaining 2 MAbs did not react with any recombinant protein expressed in E. coli. These results indicate that the fusion CEA-proteins expressed in E. coli are useful in the localization of the epitopes on the polypeptide chains when they reacted with the MAbs tested. However, one third of the epitopes of CEA peptides may be profoundly affected by the presence of disulfide bonds and/or sugar chains which do not seem to be formed well in E. coli.

Epitopes predominantly retained on the carcinoembryonic antigen molecules in plasma of patients with malignant tumors but not on those in plasma of normal individuals.

We have previously reported that a group of monoclonal antibodies (MAbs) to carcinoembryonic antigen (CEA), designated Group F MAbs, are able to discriminate CEA in tumor tissues from normal fecal antigen-2, a soluble form CEA-counterpart in normal adult feces, and that the protein epitopes recognized by them are present on the domain A3-B3 of the CEA molecule. In this study, we further investigated the molecular localization of the epitopes recognized by the Group F MAbs using three new recombinant CEA proteins with restricted domain structures expressed in Chinese hamster ovary cells, and found that the epitopes for the Group F MAbs are present on domain B3 close to the anchoring device of the CEA molecule. The epitopes for the Group F MAbs were retained on the CEA molecules in the plasma of patients with malignant tumors and on the CEA molecules spontaneously released into the culture media from established tumor cell lines. However, a large part of the CEA molecules in the plasma of normal individuals were found to lack the epitopes for the Group F MAbs. These results provide a basis for the improved cancer diagnosis by using our CEA assay system utilizing a Group F MAb, and indicate the potential clinical utility of the Group F MAbs.

Antitumor effect of methionine-depleting total parenteral nutrition with doxorubicin administration on Yoshida sarcoma-bearing rats.

Methionine-depleting total parenteral nutrition (methionine-depleting TPN), which infuses an amino acid solution devoid of L-methionine and L-cysteine as the sole protein source, showed enhancement of the effect of several anti-cancer agents. In this study, the combined effect of the methionine-depleting TPN with the administration of doxorubicin was examined in Yoshida sarcoma (YS)-bearing rats with regard to effects on the primary tumor growth, the extension of metastasis, and the host animal's life span. In the first experiment, immediately after receiving methionine-depleting TPN for 8 days, the animals were killed. Pathologic findings evaluated tumor growth in the implanted site and extension of the metastasis. In the second experiment, the survival period was determined after animals received methionine-depleting TPN for 10 days, with subsequent oral feeding until they died naturally. Proliferation of YS was markedly suppressed. In particular, hematogenous metastasis, which is a characteristic of YS, was suppressed, and a longer survival period (42.7 +/- 15.6 days, mean +/- SD) was attained in rats in the group treated with the methionine-depleting TPN combined with the administration of doxorubicin.

Epitope mapping of the carcinoembryonic antigen with various related recombinant proteins expressed in Chinese hamster ovary cells and 25 distinct monoclonal antibodies.

Antigenic epitopes of carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen (NCA) were analysed in relation to their domain structures [domains N, I (A1-B1), II (A2-B2), III (A3-B3) and M for CEA and domains N, I (A1-B1), and M for NCA]. We reconstructed cDNAs for CEA-N, CEA-N-I, CEA-N-I-II, CEA-N-I-II-III-M (CEA-whole), NCA-N, NCA-N-I and NCA-N-I-M (NCA-whole), which were expressed in Chinese Hamster Ovary (CHO) cells. The recombinant proteins were purified by immunoadsorption and gel filtration. Their mol. wts judged from Western blotting were 17,000-26,000 for CEA-N, 70,000 for CEA-N-I, 150,000 for CEA-N-I-II, 165,000 for s-CEA-whole which was spontaneously released from cells into culture medium, 180,000 for p-CEA-whole which was solubilized with phosphatidylinositol specific phospholipase C (PI-PLC) from cells, 18,000-25,000 for NCA-N, 63,000 for NCA-N-I, and 96,000 for p-NCA-whole which was solubilized with PI-PLC from cells. The divergence of the observed mol. wts from those calculated from cDNA sequences seems to indicate that these recombinant proteins are highly N-glycosylated. By enzyme immunoassays, the immunoreactivities of the purified recombinant proteins were tested with 25 distinct anti-CEA monoclonal antibodies (MAbs), each representative of 25 different subgroups within five groups (Groups 1-5) previously classified by us in terms of the reactivity with CEA and CEA-related antigens. Twenty-one MAbs previously shown to react with different protein epitopes of the CEA molecule allow to define six groups (A-F) of epitopes according to their expression by different domains of the CEA and NCA molecules. Among four epitopes common to CEA and NCA, two were found to be present on domain N (Group A) and two on domain I (Group B). Among 15 epitopes absent from NCA but expressed by CEA and normal fecal antigens (NFAs), four were on domain N (Group C), five on domain I (Group D) and six on domain II (Group E). Two epitopes were previously described as "CEA distinctive", because they were recognized by MAbs reacting with CEA but not with the NFAs. These two epitopes (Group F) were found to be expressed by p-CEA-whole but not by s-CEA-whole. The latter results suggest that the Group F epitopes are located on a part of the domain III close to the anchoring device of the CEA molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

[Notification of cancer in breast cancer patients].

The notification of the name of disease is a premise for making the system of informed consent more complete in case of cancer treatment. In Japan, however, the notification of cancer can hardly be said to have an attained social consensus. Considering that the notification can ultimately improve patients quality of life (QOL), the breast cancer group of our department informs all breast cancer patients of their diseases in principle. This paper reports and discusses the results of a survey by questionnaire on the notification of cancer in 100 patients with breast cancer. The notification of cancer was received favorably in 83% of the patients. For those who answered, the explanation on the notification was convincing and it accounted for 81%. An examination of background factors of patients who had not been convinced revealed that many of them were suffered from advanced cancer. After the notification, a human relationship with the family and friends aggravated few of them and improved in 30% (family) and 18% (friends), respectively. The notification of cancer was thus suggested to contribute to the improvement of QOL. Although 83% well received the notification of their own diseases, only 21% were affirmative for the notification of cancer in case of a member of the family. We medical professionals should make a further effort not to make the notification of cancer the pronouncement death but to make it an aid for patients to live better.

Anti-tumor effect of L-methionine-deprived total parenteral nutrition with 5-fluorouracil administration on Yoshida sarcoma-bearing rats.

L-methionine-deprived total parenteral nutrition (methionine-deprived TPN), infusing amino acid solution devoid of L-methionine and L-cysteine by the method of TPN as an only protein source, showed enhancement of the effect of several anti-cancer agents. In this study the combined effect of the methionine-deprived TPN with administration of 5-fluorouracil (5-FU) was examined in Yoshida Sarcoma (YS)-bearing rats, from aspects of effects on the tumor metastasis and the host animal's life span, in the following four groups treated with: methionine-deprived TPN with administration of 5-FU, methionine-deprived TPN without administration of 5-FU, L-methionine-contained TPN plus 5-FU, and L-methionine-contained TPN without 5-FU. In the first experiment, TPN was continued for 8 days in the four groups, and the anti-cancer effect of methionine-deprived TPN and administration of 5-FU based on both the growth of the primary tumor at the implanted site and the tumor metastasis was studied from the view point of pathologic findings of animals killed immediately after these treatments. In experiment 2 the survival period was examined after these treatments for 10 days with subsequent oral feeding until death. The results were as follows: proliferation of YS, transplanted subcutaneously, was markedly suppressed; particularly hematogenous metastasis, characteristic in YS, was prominently blunted then obtained an apparent longer survival period in rats treated with the methionine-deprived TPN with administration of 5-FU.

A specific heterotypic cell adhesion activity between members of carcinoembryonic antigen family, W272 and NCA, is mediated by N-domains.

The Ca(2+)-independent homotypic and heterotypic cell adhesion activities of a carcinoembryonic antigen (CEA) family member, W272 (CGM6), whose cDNA has recently been isolated from libraries of human peripheral leukocytes of apparently normal subjects (Arakawa, F., Kuroki, Mo., Misumi, Y., Oikawa, S., Nakazato, H., and Matsuoka, Y. (1990) Biochem. Biophys. Res. Commun. 166, 1063-1071) and spleen of chronic myelogenous leukemia patients (Berling, B., Kolbinger, F., Grunert, F., Thompson, J. A., Brombacher, F., Buchegger, F., von Kleist, S., and Zimmermann, W. (1990) Cancer Res. 50, 6534-6539) has been examined. Chinese hamster ovary cells transfected with the cDNA for W272, CEA, nonspecific cross-reacting antigen (NCA), and various antigens containing chimeric N-domain have been used. The W272 producers did not show homotypic binding at all but bound only to the cells expressing NCA and a chimeric CEA whose N-domain is substituted by that of NCA, indicating the major contribution of N-domain of NCA in the specific binding. The importance of the N-terminal region of NCA N-domain for the W272-NCA binding has been shown by detailed analysis using COS-1 cells producing various NCA whose N-domain are chimera of that of NCA and CEA. The strict heterotypic nature of the W272-NCA adhesion strongly suggests that the cell adhesion activities exhibited by CEA family members are not the fortuitous activity but the specific one which have some important physiological roles.

[Early phase II study of the combined use of AO-90 methionine-free amino acid solution and anticancer agents (5-FU and MMC) in patients with advanced and recurrent gastrointestinal cancer. AO-90 Study group].

Early phase II study in patients with advanced and recurrent gastrointestinal cancer was conducted from August 1986 through December 1987 to evaluate synergic effect of the combined use of AO-90 amino acid solution (free from Methionine) and anticancer agents (5-FU and MMC). Thirty five patients were subjected to the clinical evaluation according to the two criteria, i.e., the solid cancer chemotherapy direct efficacy criteria and the criteria of improvement of gastrointestinal passage disorder. Among 21 patients appropriately eligible for the direct efficacy criteria, the rate of more than partial response was 23.8% (5/21), while the rate of 27.8% (5/18) was observed in the patients who completely met the evaluation requirements. Among 14 patients with gastrointestinal passage disorder due to cancer, 57.1% (8/14) of the patients effectively responded to the therapy.

[Sequential methotrexate.5FU chemotherapy for gastric cancer--comparison between intra-aortic infusion therapy and intravenous administration therapy].

Sequential low-dose Methotrexate.5FU therapy was conducted on a total 52 cases of advanced or recurrent gastric carcinoma. Intra-aortic infusion therapy was performed in 31 cases and intravenous administrative therapy was employed in the remaining 21 cases. The two groups were compared in terms of the response rate and side effects. Thirty mg/m2 of Methotrexate (MTX) was given by bolus injection into the aorta or venous route, followed by 500 mg or 750 mg of 5FU by bolus injection 3 hours later. Twenty four hours after the injection of MTX, 30 mg of Leucovorin was given intravenously or orally. The major lesion of intra-aortic infusion group was primary site (stomach) in 10 cases, peritoneum and digestive tract in 9 cases, Douglas' pouch in 5 cases, liver in 3 cases, abdominal wall in 2 cases and retro-peritoneal lymph nodes in 2 cases. On the other hand, the major lesion of the intravenous administrative group was the primary site (stomach) in 5 cases, peritoneum and digestive tract in 6 cases, Virchow's lymph-node in one, hepatic hilus in one and lung in one. Response could be evaluated in 31 patients with intra-aortic therapy. Partial response was found in 9 cases and NC in 16. PD was found in 5 and so the rate of response was 29.0% (9/31). The major lesion of 9 responders was inoperable Borrmann's Type 4 gastric cancer in 2 cases, peritoneal recurrence with an abdominal mass in 4, recurrence in the abdominal wall in one, Douglas' pouch in one, and intestinal stenosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of von Willebrand factor and thrombin-interactive domains on human platelet glycoprotein Ib.

Platelet membrane glycoprotein Ib (GPIb) functions as receptors for thrombin and von Willebrand factor (vWF) in the presence of ristocetin. To precisely locate the domains on GPIb interacting with vWF and thrombin, we prepared several peptides that have amino acid sequences analogous to that of the GPIb alpha-chain and examined their effects on ristocetin-induced (vWF-dependent) and thrombin-induced platelet aggregations. A peptide extending from residues Asp235 to Lys262 showed the strongest inhibitory effect on ristocetin-induced platelet agglutination, and a group of overlapping peptides composed of 24-28 amino acid residues representing sequences extending from Phe216 to Asp274 was found to inhibit platelet aggregation induced by thrombin. Other peptides did not inhibit platelet aggregations. Moreover, the binding to platelets of the monoclonal anti-GPIb antibody (TM60) which had been shown to inhibit both ristocetin- and thrombin-induced platelet aggregations was strongly inhibited by a peptide extending from Asp249 to Asp274. These data demonstrate that the vWF-binding domain exists in a small region between residues Asp235 and Lys262; the thrombin-interacting domain, in contrast, is located between residues Phe216 and Ala274, with a possible center of interaction in the sequence from Phe216 to Thr240 on the GPIb alpha-chain, and thrombin binding requires a relatively strict conformation in this domain.

Effect of CGS 16949A plus tamoxifen on induced mammary tumours in rats.

The antitumour effect of CGS 16949A, an aromatase inhibitor, was investigated in rats with mammary tumours induced by 7,12-dimethylbenz[a]anthracene. A dose-dependent antitumour effect was observed after daily oral administration of CGS 16949A for 3 weeks. The tumour did not recur in the groups treated with 4.0 and 8.0 mg/kg per day. The complete remission rate increased and the time required to achieve complete remission became shorter with increasing daily doses. After daily administration for 3 weeks, a significant antitumour effect was observed in the group treated with CGS 16949A plus tamoxifen compared with that seen either with CGS 16949A or with tamoxifen alone. At the end of treatment, the group treated with CGS 16949A had significantly decreased oestradiol-17 beta and prolactin levels and increased levels of follicle stimulating hormone, but oestrone was not affected.

Cell adhesion activity of non-specific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: homophilic and heterophilic adhesion.

Cell adhesion activity of carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen (NCA) has been analysed by using CHO cells which had been transfected with cDNAs and are ectopically expressing each antigen on their surface. CEA expressing CHO tended to aggregate easily within 30 min after being suspended by trypsinization. Cell adhesion assay between 51Cr labelled cells and monolayered cells showed both homophilic and heterophilic interaction, the extent of which was CEA-CEA much greater than CEA-NCA greater than NCA-NCA. These reactions were completely inhibited by Fab' fragment of anti-CEA antibody. The results strongly suggested that CEA and NCA function as Ca++ independent cell adhesion molecules by homophilic and heterophilic interactions.

[Radical operation for carcinoma of gastric cardia--lymph node dissection by laparosternophrenotomy approach].

The adequate esophago-gastric resection and lymph node dissection can be performed without the necessity of a thoracotomy, by using the laparosternophrenotomy approach. For tumors restricted to lower esophagus of 4cm in localized tumors or 3cm in invaded tumors above the EG junction, the sternotomy approach is utilized. However, if the tumor extends to more than the above criteria, the thoracoabdominal approach must be utilized. For 14 years, 85 cases with tumor of gastric cardia were performed by sternotomy approach and 76 cases were performed by thoracotomy approach. The lymph node metastatic rate in the lower thoracic cavity was 26% in total. The lymph node metastatic rate of No. 110 was 22.6%, No. 111 was 17.4% and No. 112 was 12.5%. These results show the lymph node dissection in the lower thoracic cavity is very important in tumors of gastric cardia. The five year survival rate was 41% in patients who undergone curative operation by the sternotomy approach, and 45% in patients performed by the thoracotomy approach. According to our study of the lymph fluid stream in gastric cardia tumors using carbon, the lymph node dissection around the renal vein is important. This approach has less respiratory disturbance than the thoracotomy. This procedure is one of the best approaches for carcinoma of gastric cardia according to our criteria.