High expression of post-treatment Ki-67 status is a risk factor for locoregional recurrence following breast-conserving surgery after neoadjuvant chemotherapy.

INTRODUCTION: During the past decade, neoadjuvant chemotherapy (NAC) has been increasingly used in patients to reduce large tumors to a size eligible for breast-conserving therapy (BCT). However, the association between NAC and Ki-67 has not yet been fully elucidated. The aim of this study was to evaluate the prognostic significance of Ki-67, specifically after NAC followed by BCT, particularly in terms of locoregional recurrence (LRR). METHODS: A total 217 patients who received BCT after NAC were retrospectively analyzed. In these patients, immunohistochemistry analyses defined four tumor subtypes, Luminal A, Luminal B, Triple negative, and HER2 type. Ki-67 was examined by immunohistochemistry in both pretreatment core needle samples and post-treatment surgical excision specimens. High Ki-67 expression was defined as >20%. The prognostic factors LRR, locoregional relapse-free survival (LRRFS), and overall survival (OS) were analyzed. RESULTS: In total, LRR developed in 14 patients, and the 5 year-LRRFS was 94.2%. Post-treatment high Ki-67 expression, triple negative, the presence of lymphovascular invasion, and histological grade 3 were significantly high in LRR for prognostic factors (P < 0.05). There were significant differences in Kaplan-Meier method for LRRFS curves according to these three factors for patients receiving BCT following NAC (P < 0.05). There was a significant difference in the 5 year-OS for patients with and without LRR (41.7% vs. 93.9%, P < 0.001). CONCLUSION: Post-treatment high Ki-67 expression could be one of the important prognostic factors of LRR, and require careful follow-up on LRR at the time of surveillance.

Does dopamine block the spawning of the acroporid coral Acropora tenuis?

Most corals undergo spawning after a particular moon phase, but how moon-related spawning is endogenously regulated in corals remains unknown. The objective of the present study was to evaluate whether dopamine (DA) affects spawning in Acropora tenuis. When pieces of four A. tenuis colonies were reared under a natural photoperiod and water temperature, spawning was observed after the predicted moon phase. After exposure to water containing DA at 0.1 µM, pieces of the same colonies only released 5 to 10 bundles. Co-treatment with DA and pimozide (D1 and D2 receptors antagonist), but not domperidone (D2 receptor antagonist), induced mass release of bundles from the colonies. A cross-experiment revealed high fertilization rates between the control colonies (95%) and between the control and DA-treated colonies (90%), suggesting that gametes developed normally in coral tissue. Therefore, DA appears to have an inhibitory effect on the spawning of A. tenuis.

MEK-ERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes.

EZH2 overexpression occurs in various malignancies and is associated with a poor outcome. We have so far demonstrated that EZH2 downregulates the important genes such as E-cadherin and RUNX3 by increasing histone H3K27 trimethylation. However, the mechanism of EZH2 overexpression in various cancer cells remains unclear. In this study we carried out a promoter analysis of the EZH2 gene and investigated whether a survival signal that is upregulated in cancer cells is related to overexpression at the transcription level. We also explored the clinical relevance of the signaling pathway that leads to EZH2 overexpression in breast cancer and demonstrated that MEK-ERK1/2-Elk-1 pathway leads to EZH2 overexpression. The triple-negative and ERBB2-overexpressing subtypes of breast cancer are known to contain more rapidly proliferating breast cancer cells. The signaling pathway connected to EZH2 overexpression was associated with both aggressive subtypes of breast cancer. We show the significance that overexpression of histone modifier protein EZH2 in cancer cells and our study could pave the way for EZH2 inhibition to become an efficient treatment for more aggressive breast cancers.

Predictors of tumour involvement in remaining axillary lymph nodes of breast cancer patients with positive sentinel lymph node.

AIMS: To characterize the various clinicopathologic features in cases of breast cancer with positive sentinel lymph nodes (SLNs), in order to determine factors that might help in predicting the involvement of the non-SLNs. METHODS: A retrospective database review was performed of 726 breast cancer patients with stage 0-II, in whom SLNs were successfully identified. One hundred eighty-five of these patients showed positive SLNs, and subsequently underwent axillary lymph node dissection (ALND). These cases were divided into two groups based on the presence or absence of metastases in the non-SLNs, i.e. positive non-SLNs (NSLN+; 81 cases) and negative non-SLNs (NSLN-; 104 cases). RESULTS: Multivariate analysis revealed that a larger size of the primary tumour (>2.0cm), presence of lymphatic invasion, larger size of the largest SLN metastasis (>2mm), and a 100% metastatic rate in the SLNs (number of positive SLNs/number of harvested SLNs) were significantly associated with NSLN+. Among the cases in which all the four factors were present, 73% (30/41) were found to have NSLN+. CONCLUSION: We found four independent predictors in relation to non-SLN metastasis. Although these factors might be useful for determining the need of additional ALND, it would seem that even the presence of all of these four factors in combination may be insufficient to safely omit ALND. Thus, until further evidence is accumulated from the results of large clinical trials, ALND would still be recommended for patients with SLN metastasis.

Clinicopathological study of intrapelvic cancer spread to the iliac area in lower rectal adenocarcinoma by serial sectioning.

BACKGROUND: The role of iliac lymphadenectomy in surgery for rectal cancer remains unknown. Detailed clinicopathological data on lateral cancer extension may be needed to determine the true role of this procedure. METHODS: Seventy consecutive patients with low rectal cancer who underwent systematic iliac lymphadenectomy between 1991 and 1995 were reviewed. The iliac area was divided into five regions: (1) middle rectal root, (2) internal iliac, (3) obturator, (4) common iliac and (5) external iliac. Iliac lymph nodes that were cancer-free based on conventional pathological examination were serially sectioned at 100-microm intervals and re-examined for occult microscopic involvement. RESULTS: Occult microscopic foci were detected in five (7 per cent) of the 70 patients, and the overall incidence of lateral cancer spread was 24 per cent (17 of 70). Among patients without other sites of distant metastasis or circumferential involvement of the margin, the 5-year survival rate of those with lateral spread was 35 per cent. Although the prognosis of patients with cancer involving multiple iliac regions was poor, three of six patients with metastasis to only a single region were alive without disease at 3 years. CONCLUSION: Surgeons should be aware of the possibility of localized lateral spread, including microscopic metastasis, when determining the optimum procedure for iliac lymphadenectomy in patients with rectal cancer.

Relationship between SCL-90, Maudsley Personality Inventory and CCK4-induced intracellular calcium response in T cells.

This study examined the relationship between the Symptom Checklist 90 (SCL-90), Maudsley Personality Inventory (MPI) and cholecystokinin 4 (CCK4)-induced intracellular calcium response in T cells. Fifty-two normal volunteers were 37 males and 15 females; they ranged in age from 23 to 44 years. Measures included CCK4-induced intracellular calcium response in T cells, SCL-90 scores, and MPI. Paranoid ideation and interpersonal sensitivity in SCL-90 showed a significant negative association with CCK4-induced intracellular calcium response. Absent were sex differences and extroversion and neuroticism correlations. There were no significant differences between men and women in SCL-90 or MPI scores. There was no correlation among extroversion and neuroticism and CCK4-induced intracellular calcium response. CCKB receptor function might play a role in paranoid ideation and interpersonal sensitivity.

Allergy to laboratory animals: an epidemiological study.

A large cross sectional survey was carried out using a self administered questionnaire to examine the prevalence of laboratory animal allergy (LAA) and the factors associated with its development. Out of 5641 workers who were exposed to animals at 137 laboratory animal facilities in Japan, 23.1% had one or more allergic symptoms related to laboratory animals. The commonest symptom as rhinitis. About 70% of LAA subjects developed symptoms during their first three years of exposure. Atopy (past and family history), the number of animal species handled, and the time spent in handling correlated significantly with the development of LAA as did some types of job. A close relation between nasal symptoms and exposure to rabbits and between skin symptoms and exposure to rats were found. LAA subjects developed symptoms most quickly to rabbits.

Evaluation of a one-way airflow system in an animal room based on counts of airborne dust particles and bacteria and measurements of ammonia levels.

Air cleanliness in the working area of an animal room equipped with a conventional turbulent flow air distribution systems was compared with that in a similar room fitted with a one-way-flow air distribution system; in this, the supply air flowed from the working area through the racks of cages and was removed from the exhaust side. Before the introduction of animals, the air in the working and exhaust areas of both rooms was ascertained to be Class 100. With animals in situ, however, whereas in the turbulent airflow room both the workspace and exhaust air reached about Class 10,000 (with particle counts, bacterial counts and ammonia levels being almost the same) in the one-way-flow room, the air in the work space only went up to about Class 1000. With the addition of sliding doors or curtains in front of the rack in the one-way-flow room the work space air was maintained at Class 100 with almost no dust particles over 1 microns in size, airborne bacteria or ammonia being detectable. A comparison of all factors measured showed that whereas in the turbulent flow room the contamination of the work space air was 91% of that of the exhaust air, in the one-way-flow room it was only 47%, with curtains added this was reduced to 7% and with sliding doors to only 2%. In the latter case, contamination levels increased markedly on both sides during and immediately after cage changing, but recovered to the pre-cage changing levels within 30 min in the personnel working area and within 60 min on the exhaust side.

[Air-borne dust and its protein in laboratory animal facilities].

Atopic individuals who were exposed to dust in animal rooms for a long time were more likely than non-atopics to have animal-related symptoms. Standard skin prick tests were performed using crude antigens from dander and urine, and 75 to 100% of atopic persons had positive skin reactions. It seems that allergens in animal rooms result from air-borne dust and the dust originates in animal urine and dander. The protein content occurs as dust particles both below and above 10 micron in diameter. The dust particles above 10 micron cannot pass through face masks, so half of the dust protein is arrested under the mask, but smaller particles pass through. In order to minimize the symptoms, we need to improve the design of cages, animal rooms, experimental rooms, ventilation systems and other protective equipment.

[Effects of environmental temperature on thymus and spleen weights and lymphocytes in mice].

Thymus and spleen weights and lymphocytes in the blood were examined in mice transferred from 22 degrees C to 12 degrees C or 32 degrees C environments. After the exposure to either environment, organ weights tended to decrease. In mice exposed to 12 degrees C, the number of WBCs and mononuclear cells and the ratio and the number of T cells decreased on day 1 and/or 3 after the exposure. The number of B cells also declined on day 3, but the ratio of B cells increased on days 3 and 7. In mice exposed to 32 degrees C, the number of WBCs and mononuclear cells and the number of T cells decreased on day 1 and increased on day 7 and/or 14. The ratio of T cells declined on days 1, 3 and 7, while that of B cells increased on day 3, and the number of B cells increased on day 7. These results show that wide variations in environmental temperature affect the weights of organs and the number of cells which act on immune responses in mice.

Canine storage disease characterized by hereditary progressive neurogenic muscular atrophy: breeding experiments and clinical manifestation.

Progressive neurogenic muscular atrophy due to storage of a compound lipid in the lower motor neurons was diagnosed in 3 English Pointers that were littermates. Using 2 clinically normal littermates of these 3 affected dogs and 2 clinically normal dogs of the 2nd litter from the parents of the original 3 affected dogs as the initial breeding stock, a breeding experiment was performed, resulting in a breeding line of 26 dogs, 4 of which had the disease and 6 of which died before 3 months of age. Results indicated that the disease may have an autosomal recessive mode of inheritance. The clinical manifestation and electrophysiologic findings indicated lower motor neuron involvement in the affected dogs produced by breeding consistent with findings in the original 3 affected dogs. Upper motor neurons or the sensory system was not involved. The disease appeared to be distinct from other canine storage diseases previously reported.

[Filter efficiency of commercial face masks in capturing particles and airborne bacteria].

The filter efficiency of seven kinds of commercial face mask for particles and airborne bacteria was tested in the wash room of a laboratory animal facility. The filter efficiency of the masks was 19 to 50%, as measured by the weight of particles with diameters below 10 micron, 22 to 71% for particles of the 0.3 micron level, 47 to 90% for the 1 micron level, and 90 to 99.6% for the 5 micron level. The filter efficiency for airborne bacteria was 35 to 81%. Among these even masks tested, glasswool surgery masks, three-sheet synthetic fiber masks with and without charcoal, and 28-sheet gauze masks with glass filter showed generally high efficiency, and single-sheet synthetic fiber masks, 18-sheet of gauze masks and gas masks showed low efficiency.

[Circadian rhythm of air-borne bacteria and dust particles in a mouse breeding room].

The circadian rhythm of air-borne bacteria and dust particles in a mice breeding room was studied at 1-hour intervals on the first, third and fifth day after accommodation of the animals. The numbers of air-borne bacteria in the room increased day by day after accommodation, and showed a circadian rhythm which went down at about noon and rose with three peaks at about 20:00, 1:00 and 8:00. The numbers of dust particles tended to decrease from day to day, and they showed almost the same circadian rhythm as the air-borne bacteria. Correlations between air-borne bacteria and dust particles were not significant for each particle level on the first day, but were significant for all the particle levels of 0.3, 1, 2, and 5 microns at the third day, and were also significant at particles levels of 0.5 micron or more on the fifth day.

[The effects of fur on the thermal regulation of mice (Mus musculus)].

In order to ascertain the thermal insulation function of fur in mice, food and water intakes and rectal and skin temperatures were observed in Jcl: ICR mice and a group of the same species with their fur clipped, as well as BALB/C nu/+ and nu/nu mice. Food and water intakes increased as the ambient temperature dropped. The rectal temperature remained almost unchanged at ambient temperatures of from 18 to 30 degrees C. Skin temperatures were highest at side of the abdomen, lower at the neck, and lowest at the head. There was a tendency for skin temperatures to increase as the ambient temperature rose. The skin temperatures of mice with fur were higher than those of mice without fur. The thermal insulation of fur was 0.25, 0.14 and -0.06 clo at 18, 22, 26 and 30 degrees C in ICR mice, and 0.36, 0.01, 0.01 and -0.03 clo at 18, 22, 26 and 30 degrees C in BALB/C mice, respectively. These results confirm that heat loss from the skin at low temperatures could be prevented by the presence of fur. It also appeared that the hairless mice mutant had a lower metabolic rate than the animals with their fur clipped.

[Influence of blood pressure control on delivery in pregnant rats in a warm environment].

The relation between blood pressure and delivery in pregnant rats was investigated when the blood pressure of pregnant rats was controlled by a pressor or antihypertensive drug in the middle or final stage of pregnancy. All of the pregnant rats studied delivered in a 23 degrees C environment in spite of blood pressure control by a pressor or antihypertensive drug. At 33 degrees C, the pregnant rats were divided into two groups whose blood pressure was increased severely (160-175 mm Hg) or moderately (145-155 mm Hg) at 10 days of pregnancy. Those in the former group delivered, but those in the latter died in the final stage of pregnancy. When the pregnant rats in the group with high blood pressure on day 10 were treated with a antihypertensive drug in the middle stage of pregnancy or with a pressor drug in the final stage, the mortality rate was 100 per cent in both cases. The delivery rate was 57 per cent when the pregnant rats were treated with a antihypertensive drug from the middle to the final stage of pregnancy. In the group with low blood pressure on day 10, all of the pregnant rats delivered when they were treated with a pressor drug in the middle stage of pregnancy. However, the delivery rate was 89 per cent when the pregnant rats were treated with antihypertensive drug in the final stage of pregnancy.