Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig\u27s epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon.福岡歯科大学2019年

MLH1-mediated recruitment of FAN1 to chromatin for the induction of apoptosis triggered by O6-methylguanine

O6 -Methylguanines (O6 -meG), which are produced in DNA by the action of alkylating agents, are mutagenic and cytotoxic, and induce apoptosis in a mismatch repair (MMR) protein-dependent manner. To understand the molecular mechanism of O6 -meG-induced apoptosis, we performed functional analyses of FANCD2 and FANCI-associated nuclease 1 (FAN1), which was identified as an interacting partner of MLH1. Immunoprecipitation analyses showed that FAN1 interacted with both MLH1 and MSH2 after treatment with N-methyl-N-nitrosourea (MNU), indicating the formation of a FAN1-MMR complex. In comparison with control cells, FAN1-knockdown cells were more resistant to MNU, and the appearances of a sub-G1 population and caspase-9 activation were suppressed. FAN1 formed nuclear foci in an MLH1-dependent manner after MNU treatment, and some were colocalized with both MLH1 foci and single-stranded DNA (ssDNA) created at damaged sites. Under the same condition, FANCD2 also formed nuclear foci, although it was dispensable for the formation of FAN1 foci and ssDNA. MNU-induced formation of ssDNA was dramatically suppressed in FAN1-knockdown cells. We therefore propose that FAN1 is loaded on chromatin through the interaction with MLH1 and produces ssDNA by its exonuclease activity, which contributes to the activation of the DNA damage response followed by the induction of apoptosis triggered by O6 -meG.福岡歯科大

Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits.

Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.</p

Surgery for older patients with advanced esophageal cancer involving the adjacent organs.

The treatment for thirty three advanced carcinoma of thoracic esophagus with cancer infiltrations to the adjacent organs were clinically analysed. The most affected organs were the aorta, followed by the trachea and bronchus. Clinical features are that two or three organs are affected at the same time and only one organ involvement is rare in frequency. Furthermore, nodal involvement is commonly accompanied and is spreading to the mediastium and abdomen. Surgical outcome of combined resection with involved organs is now unsatisfactory. In contrast, to relieve severe symptoms and to ensure the quality of life, aggressive combined resection is indispensable. It is assumed that further advances in improvement of potent anticancer drugs and surgical techniques may lead to prolonged survival of advanced esophageal cancer patients

Postoperative Complications and Mortality of the Patients with Esophagectomy for Esophageal Carcinoma

Between 1970 and 1989, 154 patients underwent esophagectomy for esophageal cancer in our department. One hundred and twenty-one patients underwent esophageal resection and reconstruction and 14 had esopahgectomy alone without reconstruction. There were 26 operative deaths within 30 days after operation. However, the mortality rate was 29.1% during the 1970 to 1979 period, and 10.1% after 1980. Predominant postoperative complications were anastomotic leak, pneumnia, sepsis and recurrent laryngeal nerve paralysis. The rates of postoperative complications during 1970 to 1970, was 67.3% and was 43.3% after 1980. The rate of anastomotic leak was 45.4% in the former years, but it improved to 26.6% in the later period. To prevent the postoperative complications, careful perioperative management of the patients are essential

Thymectomy for myasthenia gravis

The effect of thymectomy on elimination of a myasthenic symptom was clinically evaluated. The operative approach was primarily extended thymectmy of choice via midsternotomy in all but one of transcervical approaches. Most of them belonged to Osserman II b and II a of the disease type. Thirteen cases were in combination with thymoma and thirty-five were not in combination. Thymectomy yields a 53.8% effectiveness rate for patients with thymoma and a 65.7% for patients without thymoma. There was no defenitive relationship between the operation effectiveness and the suffering duration of time. However, aggravation and no improvement of a clinical sign after thymectomy were observed in patients with a severe or moderate degree of germinal center formation

Risk Factor for Recurrence of Breast Cancer

The risk factors of recurrence following surgical treatment for patients with breast cancer were clinically evaluated on the basis of a result of clinical analysis. In this study, it is emphasized that special attention should focus on tissue CEA and DNA analysis. In conclusion, clinical uses of tissue positive CEA and aneuploid pattern in analysis of nuclear DNA content in cancer cells are of great value to forecast recurrence

Surgery for Tracheal Stenoses

On the basis of an analysis in the outcome of tracheal surgery, it proved useful for the relief of respiratory distress. As a result, we are confident that surgical management should be mandatory for tracheal stenoses, provided that the patient\u27s general condition is satisfactory with preoperatively meticulous cares. The incidence of occurring the risks of postoperative complications was relatively high in patients with malignant lesion. It seemd preferable to select a wide resection as far from the visible margin of the tumor as possible, in particular, in case of adenoid cystic caricnoma

Prognosis of Node Positive Breast Cancer

The prognosis of 63 patients with breast cancer was evaluated from the standpoint of node metastasis. In this series, the number and the location of involved node failed to assess precisely in association with the prognosis of patients with breast cancer. Axillary node metastasis (Ax(+)) as well as parasternal node metastasis (ps(+)) was one of the most influential factors on the prognosis. However, it is emphasized that ps(+) dose not indicate the detrimental sign as far as dissection would be performed

Paget\u27s Disease of the Female Breast

Eight patients of Paget\u27s disease of the breast operated during 1969 and 1990 were studied. Four patients had Paget\u27s diseases confirmed to the nipple and remaining 4 patients had an associated palpable tumor. Seven patients had invasive intraductal carcinoma and only one had noninfiltrative ductal carcinoma. None of the patients without palpable mass had axillary lymph node metastasis, while three of four patients (75%) with palpable mass in the breast had axillary lymph node metastases. One patient of 4 without palpable mass died of lung cancer 19 years and 8 months after operation. Remaining 3 are alive and well 3 years, 4 years and 16 years following mastectomy. Two of 4 patients with palpable breast mass died of metastasis 6 months and 8 months after surgery. Remaining 2 are alive and well 7 months and 22 years following mastectomy