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Discussed is the case of a 50-year-old man with a well advanced esophageal carcinoma who, during his final clinical course, suddenly developed hypercalcemia (max: 15.0 mg/ml). His serum parathyroid hormone level, however, remained within normal limits. On autopsy, an extensive metastasis to many organs and lymph nodes was noted but no evidence of a bone metastasis. Nude mice bearing the same tumoral tissue were found, on autopsy, to have similarly developed hypercalcemia and cells that were cultured were found to produce an excessive amount of Prostaglandin E2 (PGE2). These findings suggest that this humoral hypercalcemia of malignancy (HHM) was caused by excessive PGE2 produced by the tumor cells, although other possible factors should be investigated.

Novel methodology and ideas which have recently been developed in the world were shortly reviewed in the field of tumor hypoxia. At subcellular level, hypoxia induces specific protein while hypoxia inhibits initiation of DNA replication. Radioresistant characteristics of hypoxic cells are questioned under two condition, i.e., post-irradiation hypoxia and chronic hypoxia in multicellular spheroids. A novel sandwich culture system can differentiate between oxic and chronic hypoxia with oxygen effect being excluded. Evidence for perfusion-limited, acute hypoxia is provided by a novel method employing vital staining and cell sorter.

Dual parameter analysis of FCM using rhodamine 123 (R 123) and propidium iodide (PI) has made it easy to estimate cell viability. PI stains only dead cells, whereas R 123 accumulates in the mitochondria of living cells which remain unstained by PI. Therefore the combination of R 123 and PI provides a more accurate estimation of cell viability than the conventional methods of dye exclusion. Cell viability has been estimated by this method in HeLa cells treated with adriamycin in vitro. The usefulness of this analysis is suggested for the evaluation of the effect of anticancer drugs on tumor cells.

The objective of this study of 27 primary lung resected cancer patients was to evaluate sequentially the cytotoxic activity against autologous and allogeneic tumor cells during the postoperative period. In patients given a complete resection, the cytotoxic activity against the autologous tumor cells during the postoperative 1-2 weeks was significantly higher than during the postoperative 4-5 weeks (P less than 0.05, Student t test). In patients given an incomplete resection, however, no significant difference was demonstrated between the postoperative 1-2 weeks and during the postoperative 4-5 weeks. In contrast, the cytotoxic activity against the PC-3 cells or K562 cells during the postoperative 4-5 weeks tended to rise in comparison to those at the postoperative 1-2 weeks all patients in any cancer stage and whatever the amount of their lung resection. The phenotype of the effector cells which mediated the cytotoxic activity to the autologous tumor cells was the monoclonal antibody OKT 3(+), 8(+), 4(-) OKM 1(-) and the cells which were cytotoxic to the K562 cells had an OKT 3(-), 4(-), 8(-), OKM 1(+) phenotype. These results suggest that the effectors which mediate cytotoxic activity to the autologous tumor cells and to the K562 cells seems to be different and a concomitant immunity may exist in primary lung resected cancer patients.

We investigated the heat-sensitivities of human normal and cancer cells at different growth conditions in vitro. We found no difference in sensitivities between normal and cancer cells at growing condition. Normal cells at confluence, however, reduced their heat-sensitivity 5-6 times than at growing condition, while the cancer cells did not. Analysis by monoclonal antibodies for hsp 70 showed the differential staining patterns between normal and cancer cells after treatment with heat (43 degrees C for 2 hours). The constitutive expression levels of hsp 70 in cancer cells were 2-3 times higher than those in normal cells. However, the degrees of hsp 70 induction by heat shock treatment in cancer cells were lower than those in normal cells. These results suggest that cancer cells may be abnormal in expression mechanisms of hsp 70.

Biological basis for the combined chemo-radiotherapy which may be required for the useful application to the radiotherapy combined with cisplatin was discussed. Experimental data have suggested that cisplatin is useful for increasing the therapeutic gain if the tumor is sensitive for cisplatin alone. However, it was revealed from our experiment that a mouse carcinoma as in human tumors contains several clones which differ in their sensitivities to both radiation and cisplatin, and further that the radioresistant clone also showed the resistance to cisplatin. It was considered from both experimental and clinical outcome that the development of more efficient assay method for drug-sensitivity as well as that of therapeutic regimens for preventing cellular proliferation of drug- or radiation-resistant subclones was important.

Thermal radiosensitization and the possible mechanism are reviewed. In vitro studies suggest that hyperthermia can enhance cell killing by radiation resulting in a steeper slope and smaller shoulder of the cell survival curve, compared to the survival were following radiation clone. Molecular studies suggest that inhibition of DNA synthesis and or repair of DNA damage by hyperthermia might be major causes of the thermal radiosensitization. When the curve is fitted by linar quadratic (L-Q) model, a increased number of beta, while relatively stable amount of alpha values are shown for survival curve to radiation combined with hyperthermia. This implies that when a larger radiation dose (greater than or equal to 4 Gy) is combined with hyperthermia, the enhancement would be greater in thermal radiotherapy.

Cytotoxic activity of human mononuclear leukocytes (MNLs) against various tumor cell-line cells was induced by irradiated B cell-line cells. Each B cell-line cell was found to have a different potentiality and time kinetics on the induction of cytotoxicity. The enhancing effect of some B cell-line cells was found to be related to the IL-2 production from the MNLs, but not related to the IFN, TNF, and LT production. An analysis of the effector cells of the B cell-activating-killer cells (BAK) indicated that the population of the major effector cells were monocytes and NK cells. These results have provided evidence that B cell-line cells are capable of enhancing nonspecific cytotoxic activity of the MNLs, and that they might be new biological response modifiers of cancer immunotherapy.

The correlation between cell survival curve and dose response curve of MN frequency following irradiations was studied using cytokinesis-block method. Both dose response curves were analyzed by linear quadratic model, i.e. SF = exp (- alpha D - beta D2) and MN frequency = aD + bD2 + c. A good correlation between alpha/beta and a/b ratios was observed in repeated paired experiments (gamma = 0.97). When the cells were treated with BUdR, alpha-type radiosensitizer, a value in dose response curve of MN frequency increased but b value did not. In 10 renal cell carcinomas, the linear correlations between cell surviving fractions and MN frequencies were observed. When radioresponses of 5 esophageal cancer cell lines were evaluated with MN assay, wide range of a/b ratios was found. These data present that MN frequency assay using CB method is available as a tool of rapid assay of radiosensitivity of cells.

Utilizing two different types of renal cell carcinoma (JRC 1; papillary pattern, grade III, JRC 11; anaplastic and alveolar pattern, grade IV) heterotransplanted in nude mice, studied: 1) chemosensitivity tests using an in vivo-like growing culture method (collagen gel-supported culture system) with 3H-thymidine up-take assay; 2) using H and E staining, serial change of each tumour in this culture system was examined during 7 days after culture start-up. The chemo-agent tested was natural human interferon-alpha (HLBI), and the doses were 10, 100, 1,000 I.U./ml. In JRC 1, significant responses to IFN (10, 100, 1,000 I.U.) were noted, but no dose dependency was observed. In contrast, in JRC 11, compared with control, a decrease of 3H-thymidine up take in each dose of IFN was observed, but no significant differences were observed between the tested groups and control. In the 3-day culture of JRC 1, the central portion contained fewer viable cells. In the 7-day, the majority of the viable cells were replaced throughout the tumour. In contrast, in the 3-day culture of JRC 11, a decrease of viability in the central portion was observed, and this tendency progressed during the period of culture. In the 7-day only two to three thin viable cell layers were observed around the cultured tumour. Consequently differences of growth features in this culture system can be seen between the different types of tumours. Thus, a more detailed examination is needed for the clinical application of this culture system.

The achievement of complete response in cancer chemotherapy is most important for prolongation of survival period and improvement of quality in patient's life. Because of the above, chemosensitivity-oriented chemotherapy is required. Human tumor clonogenic assay (HTCA) and subrenal capsule assay (SRCA) provide relatively precise in vitro and in vivo methods for determining the chemosensitivity of individual cancer patients. The success rates are 52% in HTCA and 77% in SRCA. HTCA has an initiative for an evaluation using fluid samples and SRCA can be used against lymphomas and sarcomas which show low success rates in HTCA. Until now both methods show high predictivity of drug response in clinical situation and especially high true positive rate in SRCA is striking.

The radiation response of three human neuroblastoma cell lines (GOTO, NB1M, and SINCG) has been studied in vitro, using single cells both in the exponentially proliferative and the plateau phases. The endpoint used was clonogenic cell survivals. Cell survival curves, obtained from all cell lines, were characterized by small D0 values (0.4-0.55 Gy). However, only the GOTO cells showed the lack of a shoulder in the survival curve, whereas the other cell lines, especially the SJNCG, showed a broad sized shoulder. Delayed assay experiments with SJNCG cells showed larger repairs of potentially lethal damage, both in the exponentially proliferative and plateau phases, in contrast to GOTO cells. Further, the cell capacity for a split dose recovery was greater in SJNCG cells than in the GOTO cells. It has been said that hyperfractionation radiotherapy might be a better treatment for a neuroblastoma than the conventional therapy, however, we would suggest that a modification of the radiotherapy schedule ought to depend on the type of cells, because there are cells which show broad shoulder curves and a strong capacity for repair.

It has been suggested that one of most important parameters for predicting individual tumor treatment response in both radiotherapy and chemotherapy is intrinsic cellular sensitivity of tumor stem cells. The rationale behind the hypothesis and recent progress in the method of the assay were discussed in this review article. Since there have been no clinical data for the usefulness of the radiobiological approaches in predicting the clinical outcomes, multivariate analysis of the factors affecting prognosis seems most important to determine independent prognostic indicators. Addition of the assay data in the clinical testing may significantly improve the accuracy of the prediction if they are independent of known clinical prognosticators. Close cooperation between radiobiologists and therapeutic radiologists is certainly required for this goal.

Conventional radiations such as photons, gamma rays or electrons show several physical or biological disadvantages to bring tumors to cure, therefore, more and more attentions is being paid to new modality such as fast neurons, protons, negative pions and heavy ions, which are expected to overcome some of the defects of the conventional radiations. Except for fast neutrons, these particle radiations show excellent physical dose localization in tissue, moreover, in terms of biological effects, they demonstrate several features compared to conventional radiations, namely low oxygen enhancement ratio, high value of relative biological effectiveness, smaller cellular recovery, larger therapeutic gain factor and less cell cycle dependency in radiation sensitivity. In present paper the biological effects of particle radiations are shown comparing to the effect of conventional radiations.

A 47-year-old female was admitted for a right hypochondrial pain and was diagnosed as having a hepatic tumor with a cystic lesion. After a right and a caudal lobectomy, she died of hepatic failure due to a tumoral recurrence. At autopsy, a cystic tumoral nodule, 15 x 7 cm in size, and numerous other nodules were revealed in the liver. Metastases were seen in both lungs, the left kidney, the colon, the mesenterium, the peritoneum, the diaphragm, and the para-pancreatic lymph nodes. The hepatic tumors consisted of four types of tumor cells: spindle, round, mixed (spindle and round cells), and cells with pseudoalveolar features. All tumor cells showed a positive immunohistochemical reaction to polyclonal keratin, low molecular monoclonal keratin, alpha 1 anti-trypsin, vimentin and to actin in their cytoplasms. This is considered a very rare case.

Presented is the case of alveolar cell carcinoma in a 66-year-old woman that manifested diffuse multiple cystic cavity-forming lesions with infiltrations into the lungs. An autopsy revealed a bronchiolo-alveolar cell adenocarcinoma with mediastinal metastatic lymph nodes. Most of the cavities, whose walls were microscopically lined by tall columnar tumor cells in the pattern typical of an alveolar cell carcinoma, were round-shaped and had thin walls that showed no necrosis and were filled with mucus that contained tumor cells. The majority of these cavities were characteristic tension cavities or cysts resulting from an increased in the intraalveolar pressure caused by the mucus produced by the tumor cells in the alveolar space.

This article reports on attempt to characterize the interactions of radiation and BRMs in the treatment of malignant tumor on the basis of our some experimental results. BRMs have a high possibility to enhance radiation effects on tumor cells with in a radiation field and bring some benefits to host tumor immune system with minimizing deleterious effects of irradiation to the immune responses. But it is very difficult to determine the rational design of administration of BRMs to induce the most effective interactions on relevant immune system and other host responses in the combination with radiotherapy. We should make it clear how radiation can be useful to potentiate the tumor antigenecity or antitumor immune responses.

There are three purpose in radiation therapy: (1) the increase of the local control rate, (2) the decrease of the radiation injury in the surrounding normal tissues and (3) the improvement of the QOL (quality of life) of patients in palliative treatment. The increase of local control rate is the most important in these three aims, but clinically it is difficult to obtain the statistically significant gain in local control rate, because of the heterogeneity of tumor cells in radiosensitivity. In contrast, the slope of the dose-response curve of the normal tissues is usually steep and the slight decrease of the dose produces good results. In palliative irradiation it is important to set up the new criteria to evaluate the treatment results in each situation.

Tumors as malignant as lung cancer can be cured by radiation therapy. Local control is the primary requirement for complete cure of the tumor, but the continued presence of the mass demonstrated by imaging techniques does not necessary mean persistence of viable tumor cells. The mass shadow persisting in the region irradiated at a cure dose may simply represent delayed absorption of dead cells so that the patient should be observed for at least 3 months after the therapy. This requires patience on the part of clinitians, but erroneous additional irradiation must be avoided, because excess irradiation can do harm but no good. Radiosensitivity, radioresponsiveness, and radiocurability are all independent characteristics of the tumor. In general, the effects of radiation therapy must be evaluated comprehensively in consideration of these three characteristics of the tumor. Understanding of the natural history of the disease is essential for the treatment of malignant tumors. Therapeutic approach cannot be determined if the natural history of tumor is disregarded.

We report a primary malignant mixed mesodermal tumor in the right ovary of 75-year-old woman. She was admitted to Kobe West Municipal Hospital because of an abdominal fullness and an upper abdominal pain. A laparotomy yielded yellowish-clear ascites (2,000 ml) a tumor located in the right ovary, an upper abdominal mass the size of a child's head between the stomach and the transverse colon, and disseminating small tumors of the peritoneum. The left ovary and uterus showed no particular change. Four months after the onset of her symptoms, the patient died of carcinomatous cachexia and dyspnea. On microscope examination, the tumor of right ovary showed combined features of an adenocarcinoma, an adenosquamous carcinoma and a serous cystadenocarcinoma with foci of a heterologous stromal differentiation, that is an area of immature, striated muscle cells, bone, and cartilage and undifferentiated spindle cells. Immunohistochemical stains were useful for determining elements of the tumor cells. Epithelial tumor cells were positive for cytokeratin, epithelial membrane antigen, and CEA, while mesenchymal tumor cells were generally positive for vimentin and the immature muscle cells were especially positive for desmin, actin, and myosin. Additionally, myoglobin was identified in the rhabdomyoblast. Finally, S-100 protein was present in cartilage area and partially present in the adenocarcinomatous element.

Reported is the case of a 66-year-old woman who complained of a pain in the upper abdomen. A barium enema revealed a stenosis in the transverse and sigmoid colon and since her ileus worsened, an emergency operation was performed, which revealed an unresectable transverse colon cancer with a diffuse peritoneal metastases. After closing the wound, the patient was treated with local thermotherapy of the abdomen using an RF wave in combination with chemotherapy and immunotherapy. Later, since the tumor could not be palpated and the tumor markers dissipated, a reoperation was performed, and it was found that diffuse metastases had completely disappeared from the peritoneum. Further, a histopathological study did not disclose any tumor cells. Therefore, as the cancer was remarkably reduced, a partial transverse and descending colon colectomy was performed.

Reported is the case of an undifferentiated carcinoma of the esophagus that had developed in an 80-year-old man. This polypoid a tumor was an elevated nodular mass, 9 x 5 cm in diameter, that had invaded the muscle layer. Microscopically, the tumor was composed of small polygonal cells with hyperchromatic nuclei that were unaffected by either Grimelius or PAS staining. An epidermal growth factor immunoreactivity was found in a few of the tumor cells. Ultrastructurally, the tumor cells had abundant ribosomes, a rough endoplasmic reticulum, and mitochondria. Coamplification of HST-1 or INT-2 genes was not observed by slot blot analysis. The patient is now well with no evidence of a tumor recurrence or a distant metastasis 11 months after surgery.

Collagen types I, III and IV and procollagen III peptide (P III P) were examined immunohistochemically in 38 papillary carcinomas of the thyroid. The immunoreactivity to both type I and type III collagen was diffuse and abundantly observed in the fibrous stroma, where it displayed a fibrillar and/or granular pattern with little difference in the intensity of the staining. The immunoreactivity to collagen type IV was localized in the basement membrane of the vessels and partly in the tumor cell nests. A distinctive cytoplasmic immunoreactivity to P III P was observed in the cancer cells and the fibroblasts in all of the 38 papillary carcinomas, specifically an intense and extensive immunoreactivity by the cancer cells present in tumors having fibrosclerosing stroma and/or showing an extensive local invasion. Thus, it is conceivable that stromal collagen in a papillary carcinoma can be produced by not only the fibroblasts but also by tumor cells and its productivity could be affected by the degree of the tumoral invasion.

A developmental protein GP68 is known to appear stage-specifically in the developmental mouse brain. The expression of GP68 in tissues of 265 various human tumors and of 2 human embryos was examined immunohistologically using specific anti-GP68 rabbit antisera. Generally, endodermal, neural, and germ cell tumors were most frequently positive, while mesenchymal tumors were mostly and ectodermal tumors were intermediate. Anti-GP68 also gave positive reactions with some of non-neoplastic cells of cancer patients generally to lesser extents than neoplastic cells. Muscle and bone tissues of a 4-week-old embryo were weakly positive. Some tumors that were negative for CEA and AFP were strongly positive for GP68. The expression of GP68 in human tumor cells may represent an abnormal cellular gene-expression associated with the neoplastic change of the cell.

The expression of human aldolase A in tissues of cancer patients was examined immunohistologically using 4 monoclonal antibodies (1A2, 3C5, 1D1 and 4C2) to human aldolase A. In frozen sections, but not in paraffin sections, tumor cells of 22 out of 30 patients and non-neoplastic cells of 11 out of 21 patients examined reacted with 1A2 irrespective of cancer types. Positive reactions were seen mostly in the nucleus and some in the cytoplasm. Only tumor cells in a few neoplastic tissues gave positive cytoplasmic reactions with 1D1 or 4C2. No positive reaction was observed with 3C5. Antigens cross-reactive with aldolase A may be expressed more frequently in tumor cells than in non-neoplastic cells of cancer patients.

An 83-year-old man suffering from general malaise and discomfort in the epigastrium was admitted to hospital. On testing, peripheral blood and bone marrow smears disclosed a number of abnormal lymphocytoid cells, and a CT and a linear echo scan revealed splenomegaly and a multiple intraperitoneal lymphadenopathy, although no superficial lymph nodes were palpable. Further, abnormal lymphocytoid cells were positive for B1, B4, OKIa1, Leu1, Tac, anti-IgM, anti-IgD, and anti-lambda. Thus, a diagnosis of malignant lymphoma of the intermediate B-cell type was made. Surprisingly, serological examination reveared extremely high titers of EB-virus associated antibodies (VCAIgG 20, 480x, VCAIgA 320x, EAIgG 2,560x), but no EBNA or virus particles were detected in the tumor cells, so that no direct relationship was established between the development of the tumor and the EBV infection.

The subject was an 85-year-old woman, who had been diagnosed as having an ovarian cancer and carcinomatous peritonitis and had been treated conservatively. She subsequently died from respiratory and renal insufficiency, and the autopsy that followed revealed that her pelvic cavity had been filled by a tumorous mass that size of a child's head. Histologically, the tumor was a serous cystadenocarcinoma of the ovary. Moreover another tumor, also the approximate size of a child's head, was found sited extramurally, beneath the posterior wall mucosa of the stomach body. Histological inspection of this tumor revealed a proliferation of round oval, and spindle-shaped tumor cells. A vacuolation of the cytoplasms and karyomitosis to the extent of 10/50 HPF also were observed. Based on the findings of being positive for Vimentin and a negative EMA, this tumor was diagnosed as being a malignant leiomyoblastoma of the stomach smooth muscle. The leioblastoma is a relatively uncommon neoplasm, and recent advances in immunohistochemical staining have indicated that some of these tumors are not only of smooth muscle derivation but also of nerve origin. Therefore, this tumor, given its morphological characteristics, had been generalized in this case as a gastric stromal tumor, and with negative findings for Desmin and S-100 protein, as well as positive for Vimentin.

An immunohistochemical identification of a human lung adenocarcinoma antigen and a gastric carcinoma antigen, detected by means of the monoclonal antibodies (MoAbs) KM-93 and KM-231, respectively, has been investigated in cases of a Warthin's tumor and in normal salivary glands. The ductal basal cells of the excretory duct epithelium in normal salivary glands are characterized by their positive staining to MoAb KM-231, whereas MoAb KM-231 staining is confined to basal tumor cells in cases of Warthin's tumor. Further, MoAb KM-93 staining is slightly positive when luminal tumor cells are present. These results suggest that the histogenesis of Warthin's basal tumor cells might originate in the excretory duct epithelium.

The expression of EGF receptor, c-neu oncogene product, and of transferrin receptor in 13 cases of chordomas (9 without metastasis and 4 with metastasis) was examined immunohistologically by the B-SA method using specific antibodies to these proteins. Tumor cells in 5 cases without metastasis and 3 cases with metastasis were positive for EGF receptor, those in 7 cases without metastasis and all cases with metastasis were positive for c-neu product, while those in all cases were negative for transferrin receptor. These results suggest a possible link between the expression of cellular genes associated with the growth of neuroectodermal cells and the growth of chordoma known to arise from the embryonal rest of the notochord.

A 77-year-old male, complaining of epigastralgia, was admitted to hospital. An upper GI series revealed a hemispheric filling defect at the greater curvature of the lower gastric body and two submucosal tumor-like lesions of the antrum. Closer inspection revealed a tumor measuring 60 x 42 mm, with an irregular ulcer, and two submucosal tumor-like lesions with bridging folds, measuring 42 x 28 mm and 20 x 14 mm, respectively. Histologically, the microscopic features in the ulcerated tumor showed a variety of tumor cells with clear PAS-positive cytoplasms and marked atypical nuclei forming glandular structures that predominated. Additionally, a clear cell carcinoma, a papillary adenocarcinoma, a signet-ring cell carcinoma, and a choriocarcinoma were partially seen. Finally, in the submucosal tumor-like lesions, diffuse small tumor cells with scanty PAS-positive cytoplasms without granular structures were seen.

The functional and phenotypic characteristics of carcinomatous pleural or peritoneal lymphoid cells cultivated with either rIL 2 or TCGF have been investigated. The cultivation of the lymphoid cells with cytokines was initiated by a mixture of coexisting, viable carcinoma cells for 14 days. Results have indicated that cytokine-activated lymphoid cells from malignant pleural and peritoneal effusions showed considerable cytolytic activity against K562 and Daudi cells. The cell population responsible for LAK and/or CTL effector cells of TCGF-activated lymphoid cells were CD8+ CD11- cells. Further, in rIL 2-expanded cultures from pleural and peritoneal lymphoid cells, the CD4+ Leu 8- population was found to contain effector cells of cytotoxic activity against the tumor cells. It further was seen that the TCGF-activated CD8+ CD11- T cells possessed a more potent killing activity, in comparison to the rIL 2-activated CD4+ Leu8- T cells. However, rIL 2-activated lymphoid cells from ascites in liver cirrhosis (used for a control) showed a higher tumoricidal activity.

A case of an aggressive angiomyxoma of the vulva in a 38-year-old lady is reported. The tumor was gelatinous and 12 x 8 x 7 cm in size. Histologically, spindle or stellate-shaped tumor cells and blood vessels were found distributed in a myxoid stroma. It was found that the tumor cells were immunoreactive to vimentin but negative to desmin and smooth muscle specific actin. Ultrastructurally the tumor cells had an intercellular junction, an abundant, rough endemic reticulum, and intracytoplasmic filaments, but no focal densities of the filaments and the basal lamina. These findings have revealed that this tumor consisted of myofibroblastic cells resembling fibroblasts rather than myofibroblasts.

Surgically resected signet-ring cell carcinomas of the stomach have been clinicopathologically investigated. Although this type of carcinoma was found to be widely spread in the propria mucosa, a deeper invasion beyond the submucosa appeared more slowly than in other types of carcinomas. For example, the larger the early carcinoma in which the invasion was restricted to within the submucosa, the greater the incidence of a signet-ring cell carcinoma increase, especially in cases involving the mucosa. The incidence of a nodal metastasis was found to be lower than in cases of a moderately and poorly-differentiated adenocarcinoma in the early stage. However, when the signet-ring cell carcinomas invaded beyond the submucosa, the tumor cells spread rapidly and widely in the wall with a subsequent abdominal implantation, causing ascites and peritonitis carcinomatosa. It seemed likely that this deep invasion was accelerated by cellular change, such as the enlargement of nucleus, cellular atypy, and a decreased mucin production. As signet-ring cell carcinoma arise from the neck of glands and infiltrate the propria mucosae under the superficial epithelium, diagnosis by the barium enema and an endoscopic examination is very difficult in the case of small-size lesions. In lesions greater than 1 cm in diameter, these carcinomas usually showed an erosive and/or ulcerated appearance.

The expression of the embryonal and of the differentiational proteins in 12 cases of chordoma and in the notochord of a 4-month-old and a 5-month-old human embryo have been examined immunohistologically by the ABC method using polyclonal antibodies to CEA, AFP, or S-100, and the monoclonal antibody to cytokeratin. It was found that S-100 was expressed in all cases of chordoma and in the notochords examined. CEA and cytokeratin also were found expressed in some cases of chordoma but not in the notochords. These proteins were found expressed more strongly in chordomas without a metastasis than in those with a metastasis. In the metastatic lesions, these proteins were expressed more strongly than in the primary lesions. The antibody to AFP reacted with neither the chordomas nor the notochords tested. These results suggest a possible link between the gene-expression of the tumor cells and the microenvironment in which they are harbored.

In order to know the myelotoxicity due to combination cancer chemotherapy, the hematologic changes in 15 patients with non-Hodgkin's lymphoma (NHL) treated with combination chemotherapy using adriamycin, cyclophosphamide, vincristine and prednisolone (ACOP protocol) were observed. From this study, it was confirmed that neutrophil leukocyte depletion is one of the most important dose-limiting factors of combination cancer chemotherapy. Our experience of autologous bone marrow transplantation for 15 patients with malignant tumors, such as NHL, small cell lung cancer, nasopharyngeal carcinoma, clearly demonstrated that cryopreserved autologous bone marrow cells can rescue cancer patients from marrow-lethal doses of drugs and irradiation and thus prompts us to establish a new protocol to eradicate tumor cells.

The case of a 4-month old boy with monophasic synovial sarcoma of the left thigh is reported. He died of pulmonary metastasis 11 months after surgical removal of the primary tumor. Histologically, the tumor was composed of densely packed, small spindle cells; there were occasional islands and clusters of polygonal cells. Ultrastructurally, the closely packed polygonal cells displayed occasional desmosomelike attachments between apposing cytoplasmic membranes of neighboring cells. Many small abortive duct-like intercellular spaces with elongated cytoplasmic filopodias were seen. These findings were suggestive of epithelial differentiation of some of the tumor cells. In general, synovial sarcoma is a disease of young adults and is rare in children.

A 62-year-old woman complaining of asymptomatic hematuria was hospitalized. Although a cytologic examination of the urine was negative, abnormal findings in the right renal pelvis by DIP, RP and CT led us to suspect a pelvic tumor, and a right nephroureterotomy was performed. Light microscopy revealed deposits of amorphous, eosinophilic material in the pelvis and proximal portion of upper ureter, however tumor cells were not found. Electron microscopy revealed that these materials were aggregates of linear, non-branching fibrils, measuring about 8 nm in diameter. Histochemically, these were seen to be consistent with amyloid, producing an apple-orange birefringence with Congo red staining under a polarized light. Alkali Congo red staining after pretreatment of KMnO4 demonstrate that this amyloid protein was composed largely of AA protein in addition to lesser amounts of non-AA protein, and a primary localized amyloidosis (amyloid tumor) was diagnosed. A clinicopathologic study that was performed on 12 cases of primary localized amyloidosis of the pelvis, including our case, also is reported.

Human tumor cells such as melanoma or glioblastoma are intrinsically radioresistant on an average than cells of more common tumors in radiotherapy such as squamous cell carcinoma or adenocarcinoma. Mean inactivation dose (D) for glioblastoma A-7 cells was 3.1 Gy for cells growing exponentially, but was 4.3 Gy for cells grown in large spheroids with hypoxic cells and PLD recovery. The D for cells of squamous cell carcinoma was about 2.1 Gy. This indicates that local control of the radioresistant tumors may be achieved if a drug showing an enhancement ratio of about 2.0. Data on our experiments with others in the literature indicate that drugs which selectively sensitize hypoxic cells and inhibit PLD recovery may be useful to increase the therapeutic ratio. Experimental evidence on a nitrosourea, ACNU has been presented for such mechanisms of the action. Multivariate analysis with Cox's model on malignant gliomas of 209 patients indicated that a significant increase in the survival time was obtained in the radiotherapy combined with ACNU.

An autopsy case of a clear cell carcinoma of the salivary gland with a cerebellum invasion and a metastasis to the lung is reported. This case has been classified as a monomorphic variant, although we were unable to demonstrate the presence of glycogens in the cytoplasm of the tumor cells. Ultrastructurally, most of the proliferating cells were immature cells with few organelles. The tumor cells were unable to be differentiated into ductal cells and myoepithelial cells. Recently, the tumor has been determined to be a low grade malignancy. Obviously, this tumor had a malignant character, with a cerebellum invasion and a metastasis to the lung.

A 22-year-old male who had been receiving insulin therapy to treat uncontrollable hyperglycemia, was diagnosed to have a carcinoid in the lower rectum. The excised tumor was 1.5 cm in diameter, and showed a yellowish-white cut surface. It did not invade into the proper muscle. Numerous glucagon immunoreactive cells were found. The tumor cells contained many rounded neurosecretory granules. After tumor excision, the patient's hyperglycemia did not return in the absence of insulin administration. We suggest that the tumor may have secreted glucagon which may have acted as an antagonist against insulin in the circulation.

A 70-year-old man was admitted complaining of dull pain in the epigastrium and umbilical region. ERCP revealed a carcinoma of the pancreas; cytological examination of the pancreatic juice and ascites showed no tumor cells. Diagnostic laparotomy was performed for lasting abdominal pain and fever. Exploration revealed ascites and adhesions. The small and large intestine were covered with a gray-white membranous substance. A large tumor invading the retroperitoneal space was seen in the head of the pancreas. Histological examination of the membranous substance showed hyalinizing fibrinoid tissue; the tumor contained carcinoma cells of the pancreas. We posit that the tumor disturbed the flow of the portal vein and lymphatic vessels, leading to the patient's clinical symptoms.

A skin tumor of a 66-year-old female was examined morphologically and immunohistochemically in relation to its histogenetic aspect. The tumor was located within the dermis and composed of compact round cells with scanty cytoplasm. Electron-microscopic study revealed the presence of dense-cored granules within the cytoplasm. Thus the tumor was thought to derive from Merkel cells. The tumor cells were positive for keratin and negative for S-100 protein by immunohistochemistry. Therefore, we posit that the tumor cells did probably not originate from the neural crest, but rather from epidermal immature cells.