Search

Because fluorine-18 fluorodeoxyglucose (18F-FDG) is an excellent tumor-localizing radio-pharmaceutical, a hand-held radiation detection probe capable of localizing an area with high 18F-FDG uptake would make radioguided surgery possible. In this laboratory study, we investigated the capability of a widely used intraoperative gamma probe with a cadmium zinc telluride (CdZnTe) detector for detection of 18F-FDG. For sensitivity tests, an 0.1- ml 18F-FDG preparation was made to act as a point source with radioactivities of 1.0, 2.0, and 3.0micro Ci (37 kBq, 74 kBq, 111 kBq). Relative transmission across the side wall of the probe and sensitivity at each source-to-probe distance were measured. For simulation studies, 2 l of 18F-FDG solution (0.02micro Ci, 0.74 kBq/ml) served as normal background. One ml of 18F-FDG was prepared to simulate tumors with radioactivities of 0.05, 0.1, 0.2, and 0.4micro Ci (1.85 kBq, 3.7 kBq, 17.4 kBq, and 14.8 kBq). The ratios of the radioactive concentration of tumor to that of the background were 2.5, 5, 10, and 20:1, respectively. The tested gamma probe was shown to be sensitive to 18F. The high-energy annihilation radiation was detected from the side wall of the probe despite application of a supplementary collimator. The count rate decreased markedly as the source-to-probe distance increased, owing to the effects of the inverse-square law. In the simulation studies, the probe detected a considerable amount of background activity. However, the measured count rate increased with the increasing source-to-background ratio. In our setting, the probe was capable of distinguishing the 18F-FDG source from the background when the source-to-background ratio was no less than 5:1. To make a surgical application feasible, however, collimation or shielding against high background radiation is necessary.

This is a compilation of the results of preventive intraarterial infusion following resection of hepatic metastasis from colorectal cancer at four surgical centers. The cases studied included two groups: A) 76 patients who underwent normal liver resection only, and B) 78 patients who underwent resection with adjuvant chemotherapy. Methods included: 1) WHF, 50 cases; 2) other methods using 5-FU, 18 cases; and 3) intraarterial infusions other than 5-FU, 10 (2 cases, outcome unknown). Survival rates for groups A and B for 1 and 5 years were 71.2, 18.9% and 91.5, 56.2%, respectively, with the rates for the intraarterial infusion group showing far better results. The 1- and 5-year survival rates in terms of infusion methods were: 1) 90.7% and 64.6%; 2) 94.4% and 39.3%; and 3) 90% and 60%, respectively, showing no remarkable differences between methods. Total doses of 5-FU were (a) less than 5 g, 7 patients (b) 5-15 g, 16 patients (c) 15-30 g, 22 patients (d) greater than 30 g, 23 patients. A comparison of 1- and 5-year survival rates shows (a) 85.7% and 17.1%; (b) 66.5% and 44.3%; (c) 100% and 62.7%; (d) 100% and 66.5%, respectively, with doses (c) and (d) showing markedly better results than the (a) dosage. From this we conclude that the group undergoing intraarterial hepatic infusion had a markedly improved prognosis compared to the group not undergoing any type of adjuvant therapy. Also, groups receiving a dosage of 15 g or greater of 5-FU showed prolonged survival rates.

Two hundred eleven cases, 27.1%, of multiple primary cancers of esophagus and other organs were found in 778 cases of esophageal cancers which were treated in our institution. Among them, double cancer accounted for 92.9%, triple cancer accounted for 6.6% and quadruple cancer for 0.5%. As for the other organ of esophageal double cancer. 59.9% of them were head and neck, 25.1% were stomach, 4.9% were colon and rectum, and remaining included liver, breast, lymphoma lung kidney etc. Head and neck cancers consisted with hypopharynx, tongue, larynx, oral floor and gingiva regarding incidence in its order. For discovering of double cancer in esophagus and other organs, 1. head and neck, stomach, colon and rectum, lung, liver etc. should be investigated preoperatively in the patients of esophageal cancer, 2. Esophagus should be examined preoperatively in the patients of these cancers, 3. Screening of esophageal cancer should be performed in the patients of high risks of esophageal cancer. As for the multiple primary cancer of esophagus and other organs, the balance of treatment should be considered to take the priority of the cancer limiting the prognosis.

Total parenteral nutrition (TPN) causes atrophy of the intestinal mucosa, resulting in the degeneration and atrophy of gut associated lymphoid tissues (GALT). This suppressive effect of TPN on GALT was examined using rats. In rats receiving TPN for 2 weeks, a decrease and atrophy of Peyer's patches and a decrease in thoracic duct lymphocytes (TDL) were observed. Daily oral administration of 1000 mg/kg PSK to the rat in the TPN group corrected the number and size of Peyer's patches, and the number of TDL and its subsets were also improved compared with the TPN group. Diminution of the S-IgA of bile and portal venous blood was noticed during TPN in rats. But the groups PSK administrated were increased the amount of S-IgA in bile and portal venous blood. The immune plasma cells in the Peyer's patches were observed, the number of the MHC-class II, T helper, and IL-2 (T CGF) positive cells were decreased in the TPN group compared with control group (PSK group). It has been concluded, therefore, that PSK is effective for improving GALT inhibition caused by TPN.

The effect of the proteoglycan biologic response modifier, PSK, on lymphocyte subsets was investigated in normal rats. Six-week-old male SPF Wistar-Imamichi rats were fed a diet containing 2% PSK. Peripheral blood lymphocytes (PBL), thoracic duct lymphocytes (TDL), and those existing in the thymus, spleen and Peyer's patches were collected for analysis of subsets of T cells, helper/inducer T (Th) cells, suppressor/cytotoxic T (Ts) cells and B cells compared with those of the control group. In the PBL, differential and absolute counts of T and Th cells were lower in the group fed PSK (the PSK group) than the control group. There was no difference in Ts cells between the groups, and the PSK group showed a higher B-cell differential count. In the case of TDL, the PSK group showed greater absolute counts of T and Th cells than the control group. In tissue lymphocytes, differential T and Th cell counts were significantly greater in the PSK group than the control group, as observed first in Peyer's patches and later in the spleen. No differences between the groups were observed in these counts in the thymus. Changes in body distribution of T and Th cells induced by PSK treatment first appeared in lymphocytes in Peyer's patches, followed by PBL and TDL, and those in the spleen. No such changes were observed in the thymic lymphocytes.

Eight mouse IgG1 monoclonal anti-Adriamycin antibodies were produced in culture and in ascites in BALB/c nude mice. The binding constant and specificity was measured by an inhibition ELISA method. The assay was an indirect method using horseradish peroxidase-labeled goat Fab' antibody and 2mM ABTS (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) containing 2.5 mM H2O2 as a color reaction reagent. The binding constant of the antibodies was 10(6) to 10(8) M-1. The antibodies possessed different specificities and affinities to the adriamycin. Though adriamycin is a low molecular weight (M.W. 579.99) hapten antigen, it possesses several epitopes as antigenic determinant sites. The antigenic epitopes of the adriamycin, which until recently were unknown, were analyzed by the monoclonal antibodies.

This study was designed to examine the optimal regimen of 5-fluorouracil (5-FU), uracil and degradable starch microspheres (DSM) to prevent the hepatic metastasis of colorectal cancer. BALB/C mice were used as a model of hepatic micrometastasis of mouse transplantable colorectal cancer, Colon 26. We intraportally administered to the mice 5-FU at a dose of 34.8 mg/kg body weight; uracil at the dose equal to, or 8 times higher than that of 5-FU in molar weight and DMS at a dose of 5 mg/kg body weight. We investigated the hepatic and serum concentrations of 5-FU and uracil and the inhibitory effect of various combinations of the three substances on hepatic metastasis. The study showed that concurrent use of 5-FU with uracil at a dose 8 times higher than that of 5-Fu could keep 5-FU concentration high in hepatic tissue and relatively low in serum. This tendency became more marked with the presence of DSM. These findings support the previous study results that uracil antagonizes breakdown of 5-FU in the liver and with the aid of DSM, retards excretion of 5-FU from the liver. Further investigations for clinical application of this method will lower the incidence of hepatic metastasis of colorectal cancer.

The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver.

Four kinds of small molecular weight haptens, Desmosine, Adriamycin, 4'-carboxycotinine and 5'-Fluorouracil were used as the immunizing antigens to obtain rabbits polyclonal antisera. All of these haptenes were conjugated to Bovine Serum Albumin (BSA) using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDCl) reagent. The functional amino or/and carboxyl group in hapten molecules was utilized for conjugation with BSA by EDCl reagent. The hapten conjugated with BSA was mixed with Freund's Complete or Incomplete Adjuvant, and immunized to rabbits abdominal subcutaneous regions. More than 3 times immunized rabbit's antisera were evaluated the titer, and the specificity was investigated by ELISA method. The specific antisera against desmosine and adriamycin were produced. Anti-desmosine antibodies had no cross-reaction to molecular structure resemble pyridinoline. Anti-adriamycin antibodies reacted well to adriamycin and it could distinguish the differences of -epi type of adriamycin. The ELISA assay systems used here had such sensitivity. However the specificity possessing antisera against 4'-carboxycotinine and 5-Fluorouracil could not produce even though the antisera titers were elevated. The reasons why and what kinds of problems were there are discussed in this paper. For the production of the specific affinity possessing antisera, the length and distance between the carrier protein and the hapten and the shape of the functional groups were the important factors for production of the specific antisera which recognize free form hapten molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

By comparing gastric cancer tissues treated by the conventional hematoxylin and eosin (HE) staining and those by the chemical staining of immunohistologicals using monoclonal antibodies (MoAB) which recognize different carbohydrate antigens, the relation of cancer tissue patterns between the two staining methods was studied. Consequently, stainability was not seen in MoAB-FH4, AH6, FH6 and TKH2 in the cancer tissues where MoAB-SH1 responded to immunohistological staining. Likewise, each of MoAB-FH4, AH6, FH6 was found to have its own stain localization. The patterns made by immunohistological staining using MoAB showed so-called mosaicism even where the HE stain presented the same histologic form. Study of correlation between gastric cancer patterns and MoAB's localization revealed that localization of MoAB-SH1, AH6 and TKH2 was predominant in well differentiated adenocarcinoma. On the contrary, MoAB-FH4 and FH6, which are more specific, showed predominant localization in poorly differentiated adenocarcinoma of gastric cancers. Localization of MoAB-FH6 and AH6 increased as cancer grew from the early stage to the advanced stage. These results leads to this assumption: cancer, being of an isogenic carbohydrate structure at the initial stage when carcinoma in situ is generated, gains heterogeneity with the process of growth, differentiating into various directions and thus changing into a complicated carbohydrate structure.

To study the effects of a protein bound polysaccharide (PSK) on the immune system in normal animal, lymphocytes subsets of both peripheral (PBL) and thoracic duct lymphocytes (TDL) were analyzed in 6 week old male SPF Wistar-Imamichi rats before and after free feeding of forage which contained 2% of PSK. PBL and TDL were obtained at the time before, 4 weeks after and 8 weeks after administration of PSK. Age matched rats without administration of PSK were used as a control. Following the peripheral blood cell counts were carried out, lymphocytes subsets such as ratio of total T cells helper/inducer T (Th) cell, suppressor/cytotoxic T (Ts) cell and B cell were assayed using W3/13, W3/25, 0 X 8 and 0 X 4 monoclonal antibodies with laser flow cytometric technique (Orthospectrum III Orthodiagnostics). In terms of the PBL, number of total T cells and Th cells in PSK treated group were significantly lower than that of controls. However no statistical different could be obtained between these two groups in relation to the number of Ts cells and B cells. On the other hand, the number of T cells and Th cells in TDL of PSK treated groups were significantly higher than that of controls while Ts cell and B cell number did not show no apparent differences between these two groups. These findings indicate that oral administration of PSK have a potency to accelerate the transport of T cells from blood stream to lymphatic channel and also regulate their distribution in a normal healthy animals.

An inhibition enzyme-linked immunosorbent assay (Inhibition ELISA) system for adriamycin has been established. In this assay system, polyclonal anti-adriamycin antiserum produced in rabbits was used. The assay system showed sensitivity for adriamycin in the range of 0.1-2.5 micrograms/ml (0.53-4.23 nmoles per ml). This assay system was applied to analyze the cross-reactive properties of substances with chemical structures similar to that of adriamycin. The cross-reactive properties of six kinds of adriamycin derivatives (Epirubicin, Daunorubicin, Pirarubicin, Aclarubicin, SM-5887 and MX-2) against anti-adriamycin antiserum were measured. The cross-reactive properties of each derivative against the antiserum differed in accordance with the differences in the position of their functional groups attached to the anthracyclic ring. The antiserum recognized the -epi type of -OH group at the -4' position on sugar chains as well as number of sugar chains attached to the anthracyclic ring, and it also recognized the glycoloyl or acetyl and/or ethyl group at position 9 on the anthracyclic ring. With this assay system, the antigenic determinant sites of the anticancer drugs were inferred.

A DNA-binding protein with a molecular weight of 64,000 (64DP) has been found in elevated concentrations in the serum of patients with malignant diseases. 64DP has been found to be different from any previously described tumor markers, such as AFP, CEA, and C3DP. The results obtained with column SDS - polyacrylamide gel electrophoresis are as follows. 64DP is normally present in the serum at the concentration of 48 +/- 26 micrograms/ml (n = 49). The mean value of 64DP in 96 patients with untreated malignant disease was 167 +/- 67 micrograms/ml, whereas in 41 patients with nonneoplastic disease it was 61 +/- 23 micrograms/ml. No organ or tissue specificity seems to be required for malignant neoplasms to result in elevated serum 64DP concentrations. The clinical stage of the disease does no have much effect on the levels of 64DP and, even with histologically proven early lesions, the patients showed elevated levels of serum 64DP. Following successful surgical resection, 64DP tends to fall toward the normal value. Purification of 64DP was performed and its physicochemical properties have been defined. 64DP is a glycoprotein present in the alpha1-globulin fraction and it is rich in leucine, glutamic acid, and aspartic acid in its amino acid composition. More recently, using purified 64DP preparation, a single radial immunodiffusion assay system has been developed. According to the results of this method, the diagnostic accuracy of 64DP appears to be somewhat low and even marginal for certain types of commonly encountered surgical malignancies. Studies concerning the discrepancy between the results obtained by the two assay methods are now in progress.

Serum IAP and IS levels were studied in patients with stomach cancer. We found that the serum levels of IAP and IS increased as the disease progressed; their true positive rates as tumor markers were 49.3% and 39.8%, respectively. There was some delicate difference between these glycoproteins and T-cell subpopulation. IAP and IS correlated well with a correlation coefficient of 0.847, their value in clinical oncology are thought to be equivalent. Some difference was found between their substances and ASP, this might indicate the heterogeneous nature of the circulating glycoproteins in varying cancer-bearing status.

A DNA-binding protein with a molecular weight of 64,000 (64-DP) has been found in elevated concentrations in the serum of patients with malignant diseases, and a quantitative assay system (column-SDS disc electrophoresis method) for it has been developed. The average serum 64-DP level in 49 normal controls was 48 +/- 26 microgram/ml, whereas in 96 patients with untreated malignant disease it was 167 +/- 67 microgram/ml. Sera from patients with non-neoplastic diseases showed normal or only slightly elevated 64-DP concentrations. No organ or tissue specificity seems to be required for malignant growths to result in elevated serum 64-DP concentration. Of particular interest was the finding that all 11 patients with early gastric carcinoma and two patients with early esophageal carcinoma, all having histologically proven pT1 lesions, showed elevated levels of serum 64-DP. Following successful surgical resection and/or chemotherapy, 64-DP tends to fall toward the normal value. Although confirmation must await the results of larger clinical trials, our preliminary results strongly suggest that 64-DP evaluated by the column-SDS disc electrophoresis method may prove to be a useful tumor marker in patients with a wide variety of malignancies.

Serial sequential sections from a single tumor were examined by immunohistological staining with several monoclonal antibodies directed, respectively, to different tumor-associated carbohydrate epitopes. Staining patterns were compared with those of conventional staining with hematoxylin-eosin or periodate/Schiff's reagent. Each tumor showed different areas of staining with different antibodies, and the combined staining map shows a clear mosaicism of antigen expression within the same tumor. For example, some areas of a given tumor were stained by FH4 (defining dimeric Le(x)), while other complementary areas were strongly stained, in a mutually exclusive manner, by SH1 (defining Le(x)), AH6 (defining Le(y)), FH6 (defining sialosyl dimeric (Le(x)), or TKH2 (defining sialosyl-Tn). Some areas were stained by two or three of these antibodies. Comparisons of the mosaic-staining patterns with cytohistological properties of tumor cells within specific areas suggested that the pattern of antigen expression is correlated with degree of differentiation; e.g., poorly-differentiated cells with severe dysplasia did not express high levels of Le(x) or Le(y) but did express sialyl-Le(x) or dimeric Le(x); on the other hand, moderately or well-differentiated tumor cells in some areas expressed high levels of Le(x) or Le(y) but lower levels of sialyl-Le(x). Areas showing strong expression of sialyl-Tn in their secretions were consistently correlated with presence of well-differentiated tumor cells, whereas secretions from normal mucosae were consistently characterized by lack of sialyl-Tn expression. It is postulated that the original in situ tumors (which had homogeneous glycosylation patterns) evolved into several spatially discrete cell populations displaying different degrees of glycosylation, reflecting stages of tumor cell differentiation and progression.

High-dose chemotherapy supported by autologous bone marrow transplantation (ABMT) was given 34 times on twenty six patients with solid tumor. Excluding 6 patients with adjuvant use and 2 patients with non-evaluable lesion, the response rate (CR + PR) of 44.4% was observed among 18 evaluable patients with advanced solid tumor. The results seem to be quite significant since many of the patients had become refractory to conventional treatments and intensity of chemotherapy was still moderate in some of the patients. ABMT following a course of chemotherapy is a promising approach of overcoming the toxic limitations of intensive chemotherapy since a dose-response relationship exists in many situations of cancer chemotherapy and ABMT appears to prevent fatal myelosuppression.

A DNA binding protein with a molecular weight of 64,000, designated 64DP, has been purified and characterized. This protein was isolated from adult human pooled serum by DEAE Sephadex column Chromatography, DNA cellulose affinity column chromatography, ammonium sulfate fractionation and Sephadex G-150 gel filtration. The final preparation of 64DP was homogeneous, as judged from polyacrylamide gel electrophoresis with or without sodium dodecyl sulfate and sedimentation experiments. Physicochemical and immunochemical properties of this protein were very similar or identical to those of alpha-1-antichymotrypsin with some differences in electric mobility and th pattern of isoelectric focusing. Furthermore, the general properties of 64DP from various sera were practically similar with the exception that isolectric focusing analysis showed microheterogeneity among 64DP purified from various sera.

The cellular localization of alpha-1-antichymotrypsin (alpha 1-ACT) was studied immunohistochemically using rabbit HRP-labeled Fab' against human alpha 1-ACT. alpha 1-ACT was found in cell nuclei of carcinomas of the stomach, liver, breast, pancreas and leiomyosarcoma and in cell nuclei of lymphoid cells infiltrated into the stomach carcinoma mass. alpha 1-ACT was not found in carcinoma cells of the colon, uterus, rectum or esophagus, or in lymphoid cells infiltrated into the rectal carcinoma mass or into inflammatory regions such as gastric ulcers or appendicitis. Further, alpha 1-ACT was not found in normal cells around the carcinoma mass or in normal tissues.

Prognosis of 43 patients with esophageal squamous cell carcinoma with pre-operative irradiation and that of 50 patients by surgical excision alone were compared by five year survival rate. The pre-operative radiation treatment comprised a daily doses of 2 Gy. given for consecutive days, up to total dosage of 40 Gy. (T.D.F.66). The operative excision was done two weeks after the the completion of the radio-therapy. In early cases (st. I, II), five year survival rate of the pre-operative irradiation group was 59.8% and 74.2% for surgical treatment alone group. In advanced cases (st. III, IV), the radiation group and surgical treatment alone group showed 21.8% and 15.1% respectively. Among advanced cases, the result in relation to the location of tumor in the esophagus was studied. In the cases which the tumor was located at the upper and middle intra-thoracic esophagus, five year survival rate in pre-operative radiation group was 21.4% versus no survivor in surgical excision alone. In contrast, five year survival rate was better by surgical treatment alone among these advanced cases located at the lower esophagus. The pre-operative irradiation treatment is indicated for esophageal cancer which is advanced and located in the upper and middle intra-thoracic esophagus.

The effect of oral lentinan, a biological response modifier, on the control of systemic immune function was studied in six-week-old male Wistar-Imamichi specific-pathogen free rats. In the lentinan-treated group, 1 mg of lentinan dissolved in 1 ml of physiological saline was administered forcibly into the stomach twice weekly for four or eight weeks. Physiological saline alone was administered in a similar fashion to the control group. Leukocyte and lymphocyte counts were made and lymphocyte subsets measured using monoclonal antibodies W3/13, W3/25, and OX8, and a laser flow cytometry system. The T-cell level, the helper/inducer T-cell level, and the suppressor/cytotoxic T-cell level were measured. The peripheral leukocyte and lymphocyte counts did not change significantly in either group during treatment. After four weeks of treatment, however, the lentinan group had a significantly higher T-cell level, helper-cell level, and helper-suppressor ratio, and a significantly lower suppressor-cell level than did the control group. No significant between-group differences in the lymphocyte subsets or the helper-suppressor ratio were noted after eight weeks of treatment. Oral administration of lentinan appears to modulate the systemic immune function through stimulation of T cells, especially helper cells. Continued administration produced less effect, possibly due to a tolerance to the effect of lentinan.

Permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia. Conventional method of tracheoesophageal anastomosis has entailed various problems. The improved technique by the authors utilized the special histological features of the situation and makes possible safe and reliable anastomosis. This technique retains the tracheal perichondrium to strengthen the anastomosed portion of the trachea, and can thus prevent suture insufficiency due to tension upon the anastomotic site.

Alkaline phosphatase [orthophosphoric monoester phosphohydrolase, EC 3.1.3.1] was purified from the mucosa of rat small intestine by butanol extraction, ethanol fractionation, gel filtration, with controlled-pore glass-10 and DEAE-cellulose column chromatography. On the gel filtration, the enzyme activity was separated into three peaks; A in the void volume, B and C at lower molecular weight positions. Enzyme A was purified to homogeneity. The activity of enzymes A, B, and C was detected even on sodium dodecyl sulfate-polyacrylamide gel electrophoresis at the position of the protein of enzyme A, which had a molecular weight of 110,000 daltons. Enzymatic properties such as pH optimum, Km value for the substrate, heat inactivation and inhibition by amino acids were the same in all three enzymes. Based on these findings, together with the elution positions on gel filtration, enzyme A was regarded as an aggregate, and enzymes B and C as dimer and monomer molecules, respectively.

Twelve patients with breast carcinoma were treated with high-dose combination chemotherapy supported by autologous bone marrow transplantation (ABMT). Seven of them had advanced metastatic disease and received 12 cours of A treatment, response rate (CR +PR) was 71.5% (CR: 1, PR: 4, NC: 2 and PD: 0) and it should be noted that all 4 patients who had received adriamycin 150 mg+5-fluorouracil 1,500 mg divided in two consecutive days or equivalent high-dose of other chemotherapeutic regimen responded (CR: 1 and PR: 3). To the therapy Five other patients received ABMT-supported adjuvant chemotherapy because of high risk of recurrence. One of them died of unrelated cause and other 4 are free of disease at 11, 14, 17 and 17 months following this treatment. A major toxicity was of myelosuppression and nadirs of neutrophils were 100-1,800 on days 9-19 (median: 400 on day 12), neutrophils recovered rather rapidly to levels of greater than or equal to 1,000, greater than or equal to 1,500 and greater than or equal to 2,000 by day 15, 16 and 17, respectively. High-dose combination chemotherapy with ABMT seemed quite effective in advanced breast carcinoma and a similar approach in adjuvant setting has also been suggested.

In 9 patients with recurrent gastric carcinoma treated with intracutaneous injections of a hemolytic streptococcal preparation of OK-432 (PIC), the T/B cell ratio, the number of IgG-Fc receptor positive (T gamma) cells, the degree of blastoid transformation of lymphocytes in response to concanavalin-A (Con-A) and phytohemagglutinin (PHA), and the activity of natural killer cells (NK) in the thoracic duct lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were measured. In thoracic duct lymph, the T cell to B cell ratio was higher than that found in peripheral blood. The proportion of T gamma cells and the natural killer cell activity was found to be considerably lower in TDL than PBL, though there was a higher degree of blastoid transformation of lymphocytes in response to Con-A and PHA in TDL. After the administration of PIC, there was no significant difference in T/B cell ratios and T gamma cell proportion between TDL and PBL, though the lymphocytic blastoid transformation in response to Con-A and PHA decreased in TDL but not in PBL. PIC administration appeared to augument natural killer cell activity in both TDL and PBL.

One hundred seventy-three patients were treated 256 times with chemotherapy supported by autologous bone marrow transplantation during the past 9 years. The two most commonly used protocols were (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg) and (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 100 mg/m2 + CDDP 100-150 mg/m2). Among 115 patients in the therapeutic setting in which two courses were usually given, 75 were evaluable and the overall response rate was 42.7% with 12.0% CR rate. Breast and pediatric groups responded well; the response rate in breast cancer was 67.9% with 21.4% CR rate. Two patients with breast cancer who had multiple distant metastases and 2 pediatric patients are now alive with NED after 5 years of the treatment and seem to have been cured. The results in adjuvant settings have also been quite promising, e.g., 79.4% 5-year survival probability among breast patients mainly in stage III. Although drops of blood cell counts to the nadirs (WBC counts: less than 100-300) could not be prevented, the periods of myelosuppression appeared to have been effectively shortened so that the patients could be safely managed with intensified general supportive measures. Platelet counts are usually less affected, but the recovery is slower than for WBC counts. There were 13 patients who died within 10 weeks of the initiation of the treatment. Two of them succumbed to sepsis, and progressive disease was the cause of death in 8 patients whose terminal phases were undoubtedly affected by some infectious problems. We have shown that there are inverse relationships between infused numbers of CFU-GM and marrow recovery judged by the duration of neutropenia and the time required for neutrophils to recover over 500. Our recent laboratory experiments testing CFU-E, BFU-E and CFU-Mk in addition to MNC counts and CFU-GM showed that vulnerabilities of marrow progenitors seem to differ from cell lineage to cell lineage. This must therefore be taken into careful consideration in pursuing marrow transplantation.