Subtype and targeted therapy for TNBC

Triple-negative breast cancer (TNBC) is a heterogenous disease. For personalized medicine, it is essential to identify and classify tumor subtypes to develop effective therapeutic strategies. Although gene expression profiling has identified several TNBC subtypes, classification of these tumors remains complex. Most TNBCs exhibit an aggressive phenotype, but some rare types have a favorable clinical course. In this review, we summarize the classification and characteristics related to the various TNBC subtypes, including the rare types. Therapeutic methods that are suitable for each subtype are also discussed. Of the intrinsic breast cancer subtypes identified by gene expression analysis, the basal-like subtype specifically displayed decreased expression of an estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) cluster. We also present results that characterize the TNBC and basal-like phenotypes. TNBC may be categorized into four major classes : basal-like, immune-enriched, mesenchymal, and luminal androgen receptor. Therapeutic strategies for each subtype have been proposed along with newly approved targeted therapies for TNBC, such as immune checkpoint inhibitors. Understanding the classification of TNBC based on gene expression profiling in association with clinicopathological factors will facilitate accurate pathological diagnosis and effective treatment selection

Light activates the adrenal gland: Timing of gene expression and glucocorticoid release

SummaryLight is a powerful synchronizer of the circadian rhythms, and bright light therapy is known to improve metabolic and hormonal status of circadian rhythm sleep disorders, although its mechanism is poorly understood. In the present study, we revealed that light induces gene expression in the adrenal gland via the suprachiasmatic nucleus (SCN)-sympathetic nervous system. Moreover, this gene expression accompanies the surge of plasma and brain corticosterone levels without accompanying activation of the hypothalamo-adenohypophysial axis. The abolishment after SCN lesioning, and the day-night difference of light-induced adrenal gene expression and corticosterone release, clearly indicate that this phenomenon is closely linked to the circadian clock. The magnitude of corticostereone response is dose dependently correlated with the light intensity. The light-induced clock-dependent secretion of glucocorticoids adjusts cellular metabolisms to the new light-on environment

Schwannoma resembling metastatic lymph node

In this report, we describe a rare case of vagus nerve schwannoma associated with esophageal cancer. A 70-year-old man visited our hospital complaining of worsening dysphagia. His upper gastrointenstinal endoscopy revealed a mass in the esophagus. A contrast-enhanced chest computed tomography also detected a 15 mm nodule attached to the tracheal membrane. This nodule was diagnosed as a metastatic lymph node. Although the primary tumor reduced after neoadjuvant chemotherapy, the nodule remained intact ; it showed fluorodeoxyglucose accumulation on positron emission tomography. We had a clinical diagnosis of stage III after neoadjuvant chemotherapy and underwent surgery. Intraoperatively, the nodule could not be detached from the right vagus nerve ; therefore, we excised the nodule along with the adjacent vagus nerve. The nodule was pathologically diagnosed as a vagus schwannoma. The nodule was not a regional lymph node metastasis of esophageal cancer. His postoperative course was uneventful, and he is currently undergoing outpatient follow-up without recurrence

Adipose tissue : Critical contributor to the development of prostate cancer

The prostate is surrounded by periprostatic adipose tissue. Although adipose tissue was thought to play limited physiological roles, it has recently been recognized as an active endocrine organ, secreting growth factors and adipokines. Epidemiologically, obesity is associated with prostate cancer progression. A major mechanism to explain the link between obesity and cancer includes the insulin and insulin-like growth factor (IGF)-1 axis, sex steroids, and adipokines. When prostate cancer cells invade periprostatic adipose tissue, adipose tissue contributes to create the tumor microenvironment, mainly via adipokine secretion. Furthermore, direct crosstalk between adipocytes and cancer cells can exist.We showed that fatty acid-binding protein 4 (FABP4) released from adipocytes was taken up into prostate cancer cells and may act as a carrier of an energy source for the invasion. Bone is an adipocyte-rich organ and is the common metastatic site of prostate cancer. In the microenvironment of bone metastases, tumor cells, osteoblasts, osteoclasts, adipocytes, and other stromal cells are interacting with one another and organizing a complex system. Thus, growing evidence implicates adipose tissue as a critical contributor to the development of prostate cancer. A deeper understanding of the mechanisms leads to more effective therapeutic strategies for prostate cancer

ヒトウニョウビョウセイ ジンフゼン デ イジ トウセキチュウ ニ キュウセイ ハッショウ 1ガタ トウニョウビョウ オ ハッショウ シタ コウキ コウレイシャ ノ 1レイ

We herein presented a case of a ７５-year-old man who was referred to our hospital for hyperglycemia in a drowsy state following a convulsive seizure after receiving hemodialysis at another clinic. He had been receiving maintenance hemodialysis for non-diabetic renal failure from the age of ７３ years. He was diagnosed with diabetic ketosis because his blood glucose level was ７０７mg/dl, HbA１c ８．３％, glycoalbumin ４０．５％, serum osmolality ３２３mosm/kg, and ３-hydroxybutyric acid ５．８ mmol/l. Continuous intravenous insulin infusion therapy was immediately initiated and was changed to intensive insulin therapy on the ７th day after his admission. He did not have metabolic acidosis or serious dehydration associated with the acute metabolic derangement observed on arrival because fluid corrections for acid-base and electrolyte imbalances in the blood had been achieved by hemodialysis prior to his referral to our hospital. ΔCPR at six minutes in the glucagon loading test was hardly affected, indicating that his endogenous insulin secretory capacity was markedly reduced. The GAD antibody was negative. He had the haplotype of HLA DR４, which is considered to reflect disease susceptibility for type１diabetes in Japanese individuals. Acuteonset type １ diabetes mellitus was diagnosed based on the diagnostic criteria for acute-onset type１ diabetes mellitus （２０１２） by the Committee of the Japan Diabetes Society. At the time of his discharge, ８ units of insulin lispro were being administered prior to each meal in addition to ２ units of insulin glargine before sleeping. He was transferred to a local clinic on the ２３rd day after his admission. Although glycoalbumin had been measured every six months in the present case, it was not useful for detecting new onset diabetes. Therefore, blood glucose measurements before dialysis need to be regularly performed, even in dialysis patients with non-diabetic renal failure, in order to detect the new onset of diabetes at an early stage

治療を中止したがん患者の回復への希望に対する看護師のジレンマ

In this study, the authors clarified experience of nurses with the dilemma toward the wish for recovery of cancer patients who discontinued treatment. An interview survey was performed for 14 nurses who had ever care cancer patients who discontinued their treatment. Experience of nurses with the dilemma toward the wish for recovery of cancer patients who discontinued treatment consisted of the following categories ;［ I am not able to respond to the patient’s wish though I want to］,［There is difference how to spend the time remained between the patient and me］,［I do not have a sufficient power to support the end of the patient’s life］,［I feel disconsolate being unable to realize the patient’s wish for recover］and［I’m a nurse. I never run from my patients］. The nurses with dilemma had experience in facing nursing cares driven by the sense of responsibility as a nurse while holding pain in their heart. Ethical problems may be underlying in this experience, and the need of team work, not individual responses, has been suggested. Therefore, support to reveal experience of nurses in daily nursing care is needed

トクシマシ イシカイ ノ ジョセイ イシ シエン ジギョウ

In recent years, an increase in the ratio of female physicians in Tokushima Prefecture, with a particularly notable rise among younger generations that has exceeded the national average, has been observed. However, these physicians continue to face severe working environments, and support measures are required for female physicians during childbirth and in the early stages of parenthood. To this end, the Tokushima City Medical Association has been involved in initiatives to support female physicians since ２００８. First, we developed “Net Joy,” a website that provides the information necessary for female physicians to continue their clinical work through a bulletin board system that offers information on topics such as employment and childcare. Furthermore, we have administered questionnaire surveys related to working environments and support systems in clinical training hospitals and compiled a booklet entitled Support Notebook for Female Physicians that is available on the Net Joy website. Since ２０１１, as post-residency training in ultrasound techniques, we have held six separate practical training seminars at the Tokushima University Hospital Ultrasound Examination Center and the Tokushima City Medical Association Hall. Since ２０１４, we have been involved in efforts to enhance its training content and develop it into a long-term program

エキスパートナースが大切にする実践

To clarify the practical approaches of nurses in cancer chemotherapy, semi-structured interviews were conducted with 10 nurses certified for cancer chemotherapy in Tokushima Prefecture. The interview data were classified into the following categories : [not neglecting any step, as failure is unacceptable], [accurately predicting the symptoms of chemotherapy, rather than simply waiting for patients to report them], [making efforts to fulfill patients' desire to live], [bearing a heavy responsibility for handling toxic drugs], and [playing a role in generalizing chemotherapy]. The results suggest that the practical approaches of nurses in cancer chemotherapy three features place importance on “achieving positive effects while minimizing risks”, “not narrowing down the scope of life”, and “reducing resistance to chemotherapy”

Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration

<p>Abstract</p> <p>Background</p> <p>Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4⁺T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4⁺lymphocytes in such patients to investigate their clinical significance.</p> <p>Methods</p> <p>CD4⁺T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4⁺lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%.</p> <p>Results</p> <p>CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4⁺lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4⁺lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period.</p> <p>Conclusions</p> <p>The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4⁺T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.</p

トクシマシ イシカイ ニオケル ザイタク イリョウ エノ トリクミ

Japan is heading toward a super-aging society at a rate unparalleled with other countries. The vast increase in demand for medical treatment and care will exceed existing social resources by 2025 when the baby boom generation becomes older than 75 years. There are concerns that this may lead to the collapse of acute medical care, break out refugee Home Medical Care, and the loss of end-of-life care facilities in various areas. Therefore, Japan is promoting the establishment of a comprehensive community care system designed to allow elderly individuals to live in their own community with dignity for as long as possible. The development of home medical care is being promoted as the core component of this system. The Tokushima City Medical Association has assessed the possible risks associated with this super-aging society that should emerge at a relatively early stage. Furthermore, the development of home medical care for the public to support community medical care is regarded as the best means of tackling future challenges. Therefore, we set up the Home Care Cooperation Committee in 2008 and have worked to develop home care in Tokushima City. The Tokushima City Medical Association participated in the Home Medical Care Cooperation Base Service of commissioned projects by the Ministry of Health, Labour and Welfare as one of 105 institutions in whole country in 2012. Since 2013, we have already been implementing this with Tokushima City administration as a subsidized institution under the three year’s Home Medical Care Cooperation Base Service which was performed by the Tokushima prefecture. This base of operations incorporates the following five mandatory directives : 1. identify solutions to multidisciplinary cooperation issues, 2. develop a multidisciplinary cooperation system and a 24-h response system, 3. raise awareness among residents, 4. educate personnel engaged in home medical care, and 5. set up a consultation service for home medical care. Because of community demands for projects to be implemented in a more area-wise appropriate manner, the Tokushima Home Care Cooperation Committee was newly established following general consensus within the association. This committee was composed of 14members not limited to individuals from medical associations ; individuals from the local government and various professions involved in home medical care were recruited and made decisions regarding operating policies. The current major challenge in Tokushima City is the lack of a means to disseminate proposed solutions for home medical care throughout the entire community. Therefore, we are promoting the establishment of multiple working groups on home medical care to tackle this challenge in the future. In addition, we intend to summarize the various challenges and their solutions that we identified during the course of our operations, draw up guidelines on home medical care based on the agreement of the local government and various professions and disseminate these guidelines throughout the community. We aim to effectively operate and from multiple levels a mutual support system between doctors who have long been working in medical associations, a multidisciplinary, conscientious cooperation system to support patients, a streamlined cooperation system for hospital admission and discharge, and a patient information sharing system utilizing ICT. These systems will be operated in parallel with our base operations. We also aim to promote the future improvement of environments in which as many family doctors as possible can examine their patients at home with ease until their patient’s final breath. This should enable us to provide high-quality home medical care equally and widely throughout the community. We hereby report the home medical care initiatives and future projects of the Tokushima City Medical Association centered on the Home Medical Care Cooperation Based Project