Impact of FOXA1 Expression on the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer

Background  

Assessing indications for adjuvant chemotherapy (CT) in patients with hormone receptor (HR)-positive/human epidermal receptor 2 (HER2)-negative breast cancer remains a challenge for oncologists. In this study, we evaluated whether forkhead-box protein A1 (FOXA1) expression was a prognostic and predictive marker for HR-positive breast cancer.     

Loss of Heterozygosity at <Emphasis Type="Italic">BRCA1</Emphasis> Locus Is Significantly Associated with Aggressiveness and Poor Prognosis in Breast Cancer

Background  

BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common.     

A New Platelet-Specific Antigen, Naka, Involved in the Refractoriness of HLA-Matched Platelet Transfusion

Serum from a thrombocytopenic patient who was refractory to the transfusions of HLA-matched platelets contained a platelet-specific alloantibody, anti-Naka. Immunofluorescence analyses revealed that the Naka antigen defined by the serum was expressed exclusively on platelets and its distribution was different from P1A1, Baka, Yuka or Yukb. Analysis by Dr. von dem Borne's group revealed the Naka was also different from Koa, Kob or Zwb. Family studies showed that the Naka antigen was inherited as an autosomal codominant trait. Its antigen frequency in the Japanese population was over 97%. The results of the enzyme immunoassay using monoclonal antibodies for antigen immobilization showed that the Naka epitope did not appear to reside on GPIIb/IIIa or Ib. The transfusions of Naka-compatible platelets improved the patient's thrombocytopenia.     

A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis

BACKGROUND & AIMS: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. METHODS: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. RESULTS: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. CONCLUSIONS: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer.     

Adaptation to different noninvasive ventilation masks in critically ill patients

OBJECTIVE:

To identify which noninvasive ventilation (NIV) masks are most commonly used and the problems related to the adaptation to such masks in critically ill patients admitted to a hospital in the city of São Paulo, Brazil.

METHODS:

An observational study involving patients ≥ 18 years of age admitted to intensive care units and submitted to NIV. The reason for NIV use, type of mask, NIV regimen, adaptation to the mask, and reasons for non-adaptation to the mask were investigated.

RESULTS:

We evaluated 245 patients, with a median age of 82 years. Acute respiratory failure was the most common reason for NIV use (in 71.3%). Total face masks were the most commonly used (in 74.7%), followed by full face masks and near-total face masks (in 24.5% and 0.8%, respectively). Intermittent NIV was used in 82.4% of the patients. Adequate adaptation to the mask was found in 76% of the patients. Masks had to be replaced by another type of mask in 24% of the patients. Adequate adaptation to total face masks and full face masks was found in 75.5% and 80.0% of the patients, respectively. Non-adaptation occurred in the 2 patients using near-total facial masks. The most common reason for non-adaptation was the shape of the face, in 30.5% of the patients.

CONCLUSIONS:

In our sample, acute respiratory failure was the most common reason for NIV use, and total face masks were the most commonly used. The most common reason for non-adaptation to the mask was the shape of the face, which was resolved by changing the type of mask employed.     

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.Periodontitis is characterized by destructive inflammation of the periodontal tissue including the gingiva, periodontal ligament, and alveolar bone, and it is considered the most pressing oral health concern today, affecting more than 78 million individuals in the United States alone (1). Importantly, this disease affects not only tooth loss, but also may impact the incidence of diabetes; cardiovascular, kidney, rheumatologic, and respiratory diseases; and even premature childbirth (2). To date, clinical approaches have been focused on abrogation of invasive bacterial species that trigger local and systemic inflammatory and immune responses (3). Specifically, the current standard of care involves debridement and is sometimes accompanied by local or systemic administration of broad-spectrum antibiotic agents (4). However, given that reestablishment of periodontal lesions is common, patients must repetitively undergo these procedures. In addition, treatment is ineffective in as much as 30% of the population (5, 6).A large body of literature now suggests that bacterial species (albeit protagonists) are secondary to the host immune response in regard to the etiology of periodontal disease progression (7–9). Specifically, various lymphocyte subsets can accumulate in the periodontium, leading to the local expression of soft tissue-destroying matrix metalloproteinases (10) (MMPs) and receptor activator of NF-κB (RANK) ligand (RANKL) (11) (the primary activation factor for osteoclasts), initiating alveolar bone resorption. Several recent reports have also shown that another lymphocyte subset called regulatory T cells (Tregs) can accumulate in the gingival tissues during periodontal disease in humans and in experimental models (12–15), and helps protect the host from harmful inflammation. However, it appears that, when Tregs are present in insufficient numbers, progression of the disease is accelerated (15).Accordingly, we sought to develop a strategy for increasing local numbers of regulatory lymphocytes through the recruitment of endogenous Tregs (16) [mimicking a mechanism tumors use to evade immune responses (17)]. Specifically, a natural gradient of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22) (16, 18), could be artificially reproduced by using controlled release from a local site. Recently, we developed polymer microspheres capable of steadily releasing CCL22 by using a model-aided design process that specifies the requisite formulation properties (such as porosity) and polymer composition (16). Importantly, this process permits the tuning of release behavior using degradable polymers such as poly(lactic-co-glycolic) acid (PLGA) that are already known to be safe and biocompatible and also exhibit a proven track record of clinical translation (19, 20). This CCL22-releasing formulation has been shown to be effective at recruiting Tregs in vitro and in vivo (16). These recruited Tregs have the potential to influence the local immunological milieu, shifting it toward homeostasis (16). Based on these observations, we hypothesized that this biodegradable, controlled-release formulation of CCL22 administered locally in the periodontium, may recruit Tregs and effectively abrogate periodontal disease symptoms without necessarily reducing local bacterial numbers. Furthermore, the presence of Tregs may actually help to balance the proinflammatory response and generate an environment that is conducive to periodontal tissue regeneration as well as bone regeneration, possibly through expression of IL-10 and osteocalcin (15).By using Actinobacillus actinomycetemcomitans (Aa)-induced murine and ligature-induced canine models, we demonstrate that the Treg recruiting formulation significantly halts the progression of periodontitis as determined by significant decreases in alveolar bone resorption (mice and dogs), as well as clinical scores of disease progression (dogs). Furthermore, in mice, our Treg recruiting formulation leads to a significant decrease in the production of proinflammatory cytokines in the periodontal tissues (along with an increase in anti-inflammatory cytokines) as well as a decrease in markers of soft and hard tissue destruction (along with an increase in markers of soft and hard tissue regeneration). Overall, the Treg-recruiting formulations described herein may serve as a tool for the study of the role of Treg in periodontal disease, and even suggest a unique treatment modality that intends to harness the body’s own sophisticated immune regulatory mechanisms through the recruitment of cells.     

Giant Mucocele of Oral Cavity as a Mucocutaneous Manifestation of Sjögren Syndrome

Two cases of Sjögren syndrome who developed a giant mucocele on the floor of the oral cavity are reported. Histological analysis revealed the dense infiltration of lymph-plasmacytic infiltration around the dilated salivary duct. Similar findings were observed in the biopsied specimens of the labial salivary gland which were consistent with the grade 4 score proposed by Chisholm and Mason's criteria. Mucocele is a common mucocutaneous disease of unknown etiology except for traumatic origin and Sjögren syndrome might be one of the important underlying disease which causes giant mucocele, especially in elderly female patients.     

Hereditary ceruloplasmin deficiency with hemosiderosis: A clinicopathological study of a japanese family

A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus, all of which appeared when they were between 30 and 50 years old. All had serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The dentate nucleus, thalamus, putamen, caudate nucleus, and liver of each one showed low signal intensities on T1- and T2-weighted magnetic resonance images. Examination of the central nervous system revealed severe destruction of the basal ganglia and dentate nucleus, with considerable iron deposition in neuronal and glial cells, whereas the cerebral cortex showed mild iron deposition in glial cells without neuronal involvement. An electron microscopic study with energy-dispersive x-ray analysis showed iron depositions in the hepatocytes, of both the neural and glial cells of the brain. We consider this a new disease entity because of the primary ceruloplasmin deficiency.     

Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 2). Combined effect on the MM102 syngeneic tumor

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.