Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy

To investigate possible effects of implantation on apoptosis, we examined the cleavage of DNA in human chorionic villi and decidua in intrauterine and ectopic pregnancy. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. A ladder pattern, characteristic of the apoptotic breakdown of DNA, was present in the villi in tubal pregnancy. High molecular weight DNA was predominant in the decidua in tubal pregnancy. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in the villous tissue, together with a significant decrease in the decidual tissue, in tubal pregnancy as compared to those in normal pregnancy. An analysis in situ revealed that apoptotic cells were predominant in the syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells were occasionally seen in normal pregnancy, and their numbers decreased in tubal pregnancy. The present study demonstrates that apoptosis occurs in the villi, but not in the decidua in tubal pregnancy, unlike the situation in normal pregnancy. Our results suggest that the implantation site might affect the occurrence of apoptotic changes in early pregnancy of humans.      

IgG inhibits the increase of platelet-associated C3 stimulated by anti-platelet antibodies

We investigated the increase of platelet-associated IgG and complement component 3 (C₃) caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events. Anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib MoAbs caused a slight increase of C₃, but not of platelet-associated IgG. In contrast, anti-CD9 and anti-Fcγ II receptor MoAbs caused an increase of both platelet-associated C₃ and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C₃. When platelet-rich plasma was treated with aspirin and prostaglandin E₁ before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C₃ was scarcely influenced. These results suggest that the binding to platelets of platelet-activating antibodies caused the increase expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG. However, the increase of platelet-associated C₃ appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C₃ caused by complement-activating antibodies, while F(ab')₂ mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C₃ mediated by anti-platelet antibodies.     

Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.     

Regression of a presumed meningioma with the antiestrogen agent mepitiostane. Case report

This 68-year-old woman underwent a distal gastrectomy for gastric cancer in August 1994. A presumed meningioma of the falx was found incidentally on a staging examination of the gastric cancer, but the meningioma was not treated with surgery. Instead, after gastrectomy the patient received tegafur as adjuvant chemotherapy until February 1996, when she was readmitted to the hospital because of loss of appetite and emaciation but with no recurrence of the gastric cancer. A computerized tomography scan obtained during this second admission showed no change in the meningioma. To improve her general condition, tegafur was discontinued and she was started on a course of the antiestrogen agent mepitiostane. Administration of mepitiostane for approximately 2 years resulted in a marked regression (73%) of the meningioma. This is the first reported case of a presumed meningioma that regressed as a result of use of the antiestrogen agent mepitiostane.     

Analysis of idiopathic thrombocytopenic purpura patients with antiglycoprotein IIb/IIIa or Ib autoantibodies

We analyzed the immunological characteristics of patients with idiopathic thrombocytopenic purpura (ITP) and antiglycoprotein (GP) IIb/IIIa or GPIb autoantibodies. Among 101 ITP patients, 32 had anti-GPIIb/IIIa and 19 had anti-GPIb autoantibodies. Thrombocytopenia was more severe in patients with anti-GPIb autoantibodies than in patients without these autoantibodies, whereas ITP patients with anti-GPIIb/IIIa autoantibodies did not develop severe thrombocytopenia. Patients with anti-GPIb autoantibodies showed significant increases of platelet-associated IgM and platelet-associated C3 in comparison with patients without the autoantibodies, despite there being no significant difference in the platelet-associated IgG levels. The lymphocyte subsets and the blastogenic response in patients with anti-GPIb autoantibodies were also significantly different from those in the patients without these autoantibodies. Furthermore, severe purpura and a poor response to prednisolone were far more common in the patients with anti-GPIb autoantibodies. Activation of the complement system and/or functional abnormalities of lymphocytes thus appear to be involved in the development of thrombocytopenia in ITP patients with anti-GPIb autoantibodies, and such antibodies may be associated with a particularly severe form of ITP.     

Hepatocellular carcinoma: a case of extrahepatic seeding after percutaneous radiofrequency ablation using an expandable needle electrode

A 2.5-cm diameter, exophytic seeding of hepatocellular carcinoma was detected by contrast-enhanced computed tomography in a 76-year-old man. He had previously undergone a radiofrequency ablation therapy with an expandable, ten-hook needle electrode for the treatment of a 1.5-cm hepatocellular carcinoma in liver segment VI. Ultrasound-guided fine needle biopsy revealed that this hepatocellular carcinoma was moderately differentiated, as initial tumor was. An additional radiofrequency ablation achieved complete ablation of this neoplastic mass on contrast-enhanced computed tomography scanning. Recurrences were not found for eight months after. To prevent tumor seeding, using thermocoagulation when retracting the needle electrode may be useful.     

Determining early gastric cancer lesions appropriate for endoscopic submucosal dissection trainees: a proposal related to curability

Endoscopic submucosal dissection (ESD) was introduced worldwide as a new treatment option for early gastric cancer. Our objective was to discuss the limited ESD reports available and to determine the lesions suitable for use in training endoscopists on which lesions are appropriate for ESD. We reviewed a series of ESD reports that have been written on various risk factors related to the resectability or curability of a variety of lesions. These published studies show that certain risk factors such as tumor size and location and the presence of ulceration are closely related to both resectability and curability. Because the combination of these risk factors resulted in a much higher risk than did any single factor, we recently established a 'risk assessment chart' to determine an individual's total risk of treatment failure for early gastric cancer that has been treated using ESD. This risk chart provides a clear indication that small, non-ulcerated lesions located in the lower third of the stomach have a high rate of curative resection and are technically less challenging if ESD is used. We suggest that trainees should gain ESD experience with such lesions before they start to perform ESD on more difficult lesion types that have a lower probability of curative resection. In addition, we suggest that this risk assessment chart is suitable for the pretreatment assessment of curability and the likelihood of successful en bloc resection.     

A case of AFP-producing gastric cancer with multiple liver metastases responding to CPT-11 and cisplatin combination chemotherapy

A case of AFP-producing gastric cancer successfully treated with CPT-11 and cisplatin combined therapy is reported together with a review of the literature. A 52-year-old male was admitted with complaints of upper abdominal pain and body weight loss. Gastric cancer with multiple liver metastases was diagnosed based on endoscopy and computed tomography findings. The patient's serum AFP level was 697,100 ng/ml and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. He was treated with a combination chemotherapy consisting of CPT-11 (70 mg/m2) on day 1 and 15, and cisplatin (80 mg/m2) on day 1, repeated every 4 weeks. The primary lesion of the stomach and the liver metastases were remarkably reduced, and the serum level of AFP decreased to 18 ng/ml after 5 cycles of this treatment. No severe side effects were seen during this treatment. This result suggests that combination chemotherapy consisting of CPT-11 and cisplatin may be effective and safe for patients with AFP-producing gastric cancer with multiple liver metastases.     

Other primary cancers occurring after treatment of superficial oesophageal cancer

BACKGROUND: Recent advances in endoscopic diagnosis and treatment have led to better prognosis for patients with superficial oesophageal cancer. The incidence of subsequent other primary cancer (SOPC) has become a new problem for patients who survive after treatment of superficial oesophageal cancer. METHODS: Between 1966 and 1998, 368 patients with superficial oesophageal cancer, histologically confirmed as squamous cell carcinoma after resection, were reviewed for the presence of SOPC. RESULTS: Among the 368 patients, 43 developed SOPC. The most frequent sites of SOPC were the stomach (11 patients) and hypopharynx (11). Subsequent cancers of the stomach and hypopharynx developed significantly more frequently in heavy smokers. The 5-year cumulative occurrence rate of subsequent cancers within the fields of endoscopy of the upper gastrointestinal tract (stomach, hypopharynx and residual oesophagus) was 15 per cent. CONCLUSION: Gastric and hypopharyngeal cancers were frequently found after resection of superficial oesophageal cancer. A history of heavy smoking at the time of initial resection may be a risk factor. To make an early diagnosis of subsequent cancers, follow-up observation by upper gastrointestinal endoscopy is important after treatment of oesophageal cancer.