Mammary adenocarcinoma was induced by administering 7, 12-dimethylbenz (a) anthracene to inbred female Fischer-344 rats. Then cell suspensions of this mammary cancer were subcutaneously inoculated into other rats of the same strain to obtain transplantable mammary cancer. The transplantable mammary cancer cells were subsequently injected into the femoral medullary cavity of other rats of the same strain to prepare a metastatic bone tumor model. The cumulative survival rate and the radiographic and histologic changes were determined after inoculation of mammary cancer cells into the femur. In addition, the effect of X-ray irradiation was assessed. At 5-7 days after mammary cancer cells were injected, periosteal spiculation appeared on radiographs. Histological examination showed prominent changes in the resting osteoblast layer lining both the endosteum and the periosteum immediately or 1 day after inoculation. In the vicinity of the tumor cells, a large number of osteoclasts were generated and bone lysis occurred. With the subsequent growth of tumor tissue, bone lysis by osteoclasts and by tumor cells was progressive. Finally, fracture and/or bone destruction occurred, followed by the death of the animals. Irradiation of the cancer cells at the site of injection into bone prolonged the life-span of the rats.
An IgG1 mouse monoclonal antibody (MoAb) to sialyl-Lewisa antigen that showed specific in vitro binding to human gastrointestinal tract tumors was obtained by the hybridoma technic. F(ab')2 fragments of this MoAb were radioiodinated and injected into nude mice bearing human colon carcinoma xenografts. The MoAb fragments accumulated specifically in the colonic tumors at 1-2 days after injection and did not accumulate in an unrelated tumor (melanoma). The tumor/normal tissue ratio and tumor/blood ratio was 2-10 fold higher in mice with F(ab')2 fragments as compared to mice injected with the intact MoAb, suggesting that the F(ab')2 fragment could be used in radioimmunoscintigraphy. Based on this favorable result, clinical application was performed in a patient with pelvic recurrence of rectal carcinoma. The radiolabelled F(ab')2 fragment produced a positive scan at 3 days after administration.
Sialyl-TN anigen (STN; NeuAc 2→6GalNac α 1-o-Ser/Thr)is a mucin-associated antigen expressed by some neoplasms. In this study, STN expression was investigated immunohistochemically in 152 patients with gastric cancer who underwent curative surgical resection. STN expression was detected in 74 of the tumors (48.7%). There was no significant relationship between STN positivity and histologic type. However, STN positivity was significantly higher in patients with lymph node metastasis than that in those without metastasis (P<0.01). In addition, STN positivity increased as tumor invasion became deeper and the STN-positive rate also became higher as the histologic stage increased. Furthermore, patients with STN-positive tumors had a significantly poorer prognosis than those with STN-negative tumors (p<0.01). Our findings suggest that STN expression is related to the depth of invasion, lymph node metastasis, and stage of gastric carcinoma and that it may be a useful prognostic factor.
Using the dextran-coated charcoal method, estrogen and progesterone receptors were measured before and after preoperative treatment in 24 patients with advanced primary breast cancer. The average estrogen receptor level fell significantly (P<0.005) after preoperative treatment, while the average progesterone receptor level did not change significantly. There was no change of estrogen receptor or progesterone receptor status from negative to positive in any of the patients. The average pretreatment estrogen receptor level was higher in the responders than in the nonresponders. The average estrogen receptor level fell significantly (P<0.03) in the responders after treatment, but it did not change significantly in the nonresponders. These results demonstrate that quantitative data on hormone receptors are more useful clinically than qualitative data. It appears that estrogen receptor levels in human breast cancer usually decrease or remain unchange after treatment and that receptor status does not change from negative to positive.
Preoperative induction chemotherapy employing anthracycline agents was performed in 21 patients with locally advanced breast cancer. The response rate of this group receiving preoperative induction chemotherapy was higher than that of 18 historical control patients receiving preoperative endocrine therapy or radiotherapy (48% vs. 28%, p<0.10). Standard radical mastectomy or extended radical mastectomy was carried out after induction chemotherapy, and 90% of the patients with stage III and inflammatory breast carcinoma underwent curative resection. There was no significant difference in survival between the two groups. However, the 50% survival duration was longer in the preoperative induction chemotherapy group than in the control group (118 months vs. 23 months). Anthracycline agents (adriamycin, epirubicin, and THP-adriamycin) were used alone or in combination with other agents for the preoperative chemotherapy. The side effects were tolerable. Systemic induction chemotherapy using anthracyclines is effective for locally advanced breast cancer as a component of multidisciplinary therapy.
The usefulness of the chick embryo assay as an in vivo chemosensitivity test was studied in the prediction of the response to combination chemotherapy regimens in clinical use for lung cancer in Japan, such as cisplatin+vindesine (PV therapy), cisplatin+adriamycin+mitomycin C (PAM therapy), and mitomycin C+vindesine+cisplatin (MVP therapy). One hundred and seventeen surgical specimens of advanced lung cancer were examined by this method. All the tumor specimens tested could be grafted on the chorioallantoic membranes of chick embryos, so the evaluation rates was 100%. In this system, the efficacy rates of PV, PAM, and MVP therapy were 16.9, 13.8, and 19.0%, respectively. The efficacy of therapy was in the following order; epidermoid carcinoma>small cell carcinoma>adenocarcinoma>large cell carcinoma>adenosquamous carcinoma. Interestingly, the effect of MVP therapy on epidermoid carcinoma was significantly high. Twenty-six patients received the same chemotherapy regimens as those tested in the chick embryo assay, and 24 of them could be evaluated for clinical response. In 4 patients, the assay correctly predicted a clinical partial response (true positive). There were no false positive results for this assay, as well as 5 false negative results and 15 true negative results. The overall predictive accuracy was 79.2%. Thus, the chick embryo assay was a good predictor of the clinical outcome. This in vivo chemosensitivity assay for lung cancer is also advantageous because of its convenience, rapidity, and low cost.
A patient with gastric carcinoma which recurred as a solitary colonic metastasis 10 years after gastrectomy is reported. The patient was a 52-year-old man who had undergone total gastrectomy and pancreatico-splenectomy (Appleby's procedure) for Type 5 gastric carcinoma. Histologic examination showed poorly differentiated adenocarcinoma invading the gastric wall to reach the serosal surface (se) with limited lymph node metastases (to n1 nodes). He remained well until 10 years after surgery, when he developed epigastric pain and abdominal distenton. Physical examination revealed a 10-cm-mass in the upper abdomen. Barium enema showed a circumferential stenosis at the midpoint of the transverse colon. Endoscopy showed the colonic mucosa was edematous and featured an irregular cobblestone pattern, that was suggestive of submucosal infiltration. Under the working diagnosis of recurrent gastric cancer, transverse colectomy was performed. Histologic examination revealed poorly differentiated adenocarcinoma that was very similar to the gastric carcinoma resected 10 years earlier. Although the tumor was transmural, it was more extensive at the serosal surface and the mucosa was intact. Judging from the mode of extension, this case was diagnosed as solitary recurrence of gastric carcinoma in the transverse colon from a microscopic tumor focus.