Establishment of a double Philadelphia chromosome-positive acute lymphoblastic leukemia-derived cell line, TMD5: effects of cytokines and differentiation inducers on growth of the cells

A double Philadelphia chromosome (Ph)-positive leukemia cell line with common-B cell phenotype, designated TMD5, was established from the blast cells of a patient with double Ph-positive acute lymphoblastic leukemia. TMD5 cells expressed 190 kDa BCR/ABL chimeric protein and 145 kDa ABL protein. The cells proliferated without added growth factors. Autocrine growth mechanism was not recognized. The addition of growth factors such as G-CSF, GM-CSF, IL-3, IL-6, or Stem Cell Factor did not affect the growth. Herbimycin A suppressed the growth of TMD5 cells at the low concentration that did not affect Ph-negative cells. It suppressed tyrosine phosphorylation of intracellular proteins in TMD5 cells. Dexamethasone and dibutyryl cyclic AMP also suppressed the growth. They, however, did not affect the phosphorylation significantly. Neither all-trans retinoic acid nor interferon-alpha affected the growth. TMD5 cells, characterized minutely here and rare in that they have double Ph chromosomes, will be a useful tool for the study of Ph-positive leukemia.     

The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation

The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100–120 mg/m² superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3 % (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2 % (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.     

Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system

To clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-μm-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer = 108 keV/μm). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena.     

Development of the irradiation method for the first instar silkworm larvae using locally targeted heavy-ion microbeam

To carry out the radio-microsurgery study using silkworm, Bombyx mori, we have already developed the specific irradiation systems for eggs and third to fifth instar larvae. In this study, a modified application consisting of the first instar silkworm larvae was further developed using heavy-ion microbeams. This system includes aluminum plates with holes specially designed to fix the first instar silkworm larvae during irradiation, and Mylar films were used to adjust energy deposited for planning radiation doses at certain depth. Using this system, the suppression of abnormal proliferation of epidermal cells in the knob mutant was examined. Following target irradiation of the knob-forming region at the first instar stage with 180-mum-diameter microbeam of 220 MeV carbon (12C) ions, larvae were reared to evaluate the effects of irradiation. The results indicated that the knob formation at the irradiated segment was specially suppressed in 5.9, 56.4, 66.7 and 73.6% of larvae irradiated with 120, 250, 400 and 600 Gy, respectively, but the other knob formations at the non-irradiated segments were not suppressed in either irradiation. Although some larva did not survive undesired non-targeted exposure, our present results indicate that this method would be useful to investigate the irradiation effect on a long developmental period of time. Moreover, our system could also be applied to other species by targeting tissues, or organs during development and metamorphosis in insect and animals.     

Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer

Background

The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck.

Methods

We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems.

Results

The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38–24.9; P?=?0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3–4 cancers.

Conclusion

The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

     

Synergistic antitumor activity of cisplatin and UFT in nude mice bearing transplantable nasopharyngeal hybridoma

Combination therapy with cisplatin (CDDP) and UFT, a drug prepared with 1-(tetrahydro-2-furanyl)-5-fluorouracil and uracil at a mixing molar ratio of 1:4, was examined in nude mice bearing transplantable human nasopharyngeal hybrid cell (A2L/AH). The tumor growth of A2L/AH was inhibited in the group administered UFT 20 mg/kg, but was not in 10 mg/kg group in comparison with the control group. An inhibition rate (IR) of the tumor growth at 20 mg/kg and 10 mg/kg doses was 80.2 and 21.3%, respectively. The group received CDDP (5 mg/kg, q7d x 3, 2 mg/kg, q7d x 3, and 1 mg/kg, qd x 6) by intraperitoneal injection, resulted in 75.2, 37.4, and 23.1% inhibitions, respectively. While, the response rate in the group treated with CDDP (1 mg/kg, qd x 6) and UFT (10 mg/kg) showed a synergistic effects (IR, 66.3%) which was higher than in the group administered CDDP (2 mg/kg, q7d x 3) and UFT (10 mg/kg) (IR, 58.3%).     

The value of intracellular CD41 antigen detection to the diagnosis of acute megakaryoblastic leukemia]

An 11-month-old boy was transferred to our hospital because of fever and bleeding tendency on March 13, 1998. Laboratory studies showed a white blood cell count of 43,360/microliter with 75% blasts, a hemoglobin concentration of 8.4 g/dl, and a platelet count of 23 x 10(3)/microliter. Surface marker analysis with a flow cytometer revealed that only 21% and 11% of the blasts, respectively, were positive for CD41 and CD42b. Treatment with a permeabilizing agent apparently increased the reactivity of the blasts with anti-CD41 monoclonal antibody (MoAb), which can recognize IIb independently of IIIa. However no significant differences were observed in reactivity with anti-CD41 MoAb (which recognizes the IIb/IIIa complex) anti-CD61 MoAb and anti-CD42b MoAb before or after fixation. Blasts positive for platelet peroxidase were observed by electron microscopy, thus confirming the diagnosis of acute megakaryoblastic leukemia. We concluded that the detection of intracellular antigens is useful for the quick diagnosis of acute megakaryoblastic leukemia characterized by low surface expression of megakaryocytic lineage antigens.