Explore the vast range of titles available.

BackgroundThe membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for gastric cancer. The present study investigated ion channel expression profiles in gastric CSCs (GCSCs).MethodsCells strongly expressing CD44 were separated from MKN74 cells, a human gastric cancer cell line, by fluorescence-activated cell sorting (FACS), and GCSCs were identified based on tumorsphere formation. Gene expression profiles in GCSCs were examined by a microarray analysis.ResultsAmong MKN74 cells, CD44 messenger RNA levels were higher in CSCs than in non-CSCs. These CSCs also exhibited resistance to cisplatin. The microarray analysis revealed that the expression of several genes related to voltage-gated Ca2+ channels (VGCCs), including CACNA2D1 and CACNB4, was upregulated. The cytotoxicities of the CACNA2D1 inhibitor amlodipine and the CACNB4 inhibitor verapamil were greater at lower concentrations in CSCs than in non-CSCs, and markedly reduced tumorsphere numbers. Tumor volumes were significantly smaller in a xenograft nude mouse model treated with amlodipine or verapamil in combination with cisplatin than in that treated with cisplatin alone.ConclusionsThe present results indicate that VGCCs play a role in maintaining CSCs, and demonstrated the potential of their specific inhibitors, amlodipine and verapamil, as targeted therapeutic agents against gastric cancer.

A sporadic E layer has significant influence on radio communications and broadcasting, and predicting the occurrence of sporadic E layers is one of the most important issues in space weather forecast. While sporadic E layer occurrence and the magnitude of the critical sporadic E frequency (foEs) have clear seasonal variations, significant day-to-day variations as well as regional and temporal variations also occur. Because of the highly complex behavior of sporadic E layers, the prediction of sporadic E layer occurrence has been one of the most difficult issues in space weather forecast. To explore the possibility of numerically predicting sporadic E layer occurrence, we employed the whole atmosphere–ionosphere coupled model GAIA, examining parameters related to the formation of sporadic E layer such as vertical ions velocities and vertical ion convergences at different altitudes between 90 and 150 km. Those parameters in GAIA were compared with the observed foEs data obtained by ionosonde observations in Japan. Although the agreement is not very good in the present version of GAIA, the results suggest a possibility that sporadic E layer occurrence can be numerically predicted using the parameters derived from GAIA. We have recently developed a real-time GAIA simulation system that can predict atmosphere–ionosphere conditions for a few days ahead. We present an experimental prediction scheme and a preliminary result for predicting sporadic E layer occurrence.

Background Malnutrition leads to accelerated tumor progression through the suppression of tumor immunity. The present study examined the significance of the preoperative prognostic nutritional index (PNI) for predicting postoperative survival outcomes in gastric cancer (GC). Methods A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte counts (per mm 3 ). The prognostic impact of preoperative PNI was examined using two multivariate analysis models. Results The optimal cutoff value of preoperative PNI for predicting overall survival (OS) was 48 based on a receiver operating characteristic curve. The 5-year OS rate was 59.5% in the PNI<48 group and 91.3% in the PNI≥48 group ( p <0.001). In the first multivariate survival analysis where all explanatory variables were composed of preoperative factors alone, a PNI<48 (hazard ratio [HR] 3.33; 95% confidence interval [CI] 2.01–5.56, p <0.001), upper-third GC and cT2–T4 were identified as independent indicators of a poor OS. In the second survival analysis where explanatory variables were composed of preoperative, intraoperative, and pathological factors, a PNI<48 (HR 2.80; 95% CI 1.65–4.78, p <0.001), hypertension, open gastrectomy, intraoperative blood loss≥100g, pT2–T4, and pN+ were independent prognostic factors. Conclusion Preoperative PNI may be a useful predictor of postoperative survival outcomes both before and immediately after surgery in GC. Appropriate perioperative interventions and the meticulous surveillance of GC relapse are necessary for patients with PNI<48.

Transthyretin cardiac amyloidosis (ATTR-CA) involves the buildup of transthyretin protein in the heart muscle in the form of amyloid fibrils, which can affect heart structure and function. Common ECG findings of ATTR-CA include low QRS voltage and a pseudo-myocardial infarction (MI) pattern, defined as pathological Q waves or QS complexes in two consecutive leads without a history of MI or echocardiographic evidence of akinetic areas. Here, we present a case of ATTR-CA in a very elderly patient, in whom pathological Q waves on ECG were true indicators of a prior inferior MI. A 96-year-old woman with a history of inferior MI presented to her primary care clinic with a one-week history of nocturnal dyspnea. She had undergone coronary stent placement in the distal right coronary artery five years earlier for inferior MI. An ECG revealed abnormal Q waves, ST elevation of 0.5 mm, and T wave inversion in limb leads III and aV , with no significant findings suggestive of left ventricular (LV) hypertrophy. Over a two-year period, QRS voltage progressively decreased in all leads, while the ST-T changes remained unchanged. Transthoracic echocardiogram (TTE) showed LV concentric hypertrophy with an increased wall thickness of 14 mm, except in the infero-septal region. In basal and mid-short-axis views, infero-septal wall motion was severely reduced, with notable wall thinning in contrast to the global LV hypertrophy observed elsewhere - findings consistent with prior inferior MI. The patient was ultimately diagnosed with ATTR-CA based on technetium-99m-pyrophosphate scintigraphy and monoclonal protein detection tests. Clinicians should recognize that pathological Q waves in ATTR-CA do not always indicate a pseudo-MI pattern. When both ECG and TTE suggest an MI pattern, further evaluation for coronary artery disease is warranted as part of the ATTR-CA diagnostic workup. In patients with both ATTR-CA and prior MI, a comprehensive clinical approach addressing both conditions is essential for optimizing prognosis.

Most herbal medicines contain licorice, which may inhibit 11-beta-hydroxysteroid dehydrogenase type 2 (11βHSD2). When licorice inhibits 11βHSD2, accumulated cortisol binds excessively to the mineralocorticoid receptor (MR) instead of aldosterone, promoting sodium absorption and potassium excretion. This condition has been called pseudoaldosteronism due to its clinical manifestations resembling those of primary aldosteronism, producing excessive aldosterone. Primary aldosteronism and pseudoaldosteronism usually present with increased urine potassium excretion in the face of hypokalemia due to excessive MR activation by aldosterone and cortisol, respectively, the so-called renal potassium loss. Here, we report an atypical case of licorice-induced pseudoaldosteronism, which unexpectedly presented with decreased urine potassium excretion in the presence of severe hypokalemia in an elderly patient. A spot potassium-to-creatinine ratio was decreased to 4.5 mmol/g creatinine. A 24-hour urine collection also revealed decreased urine potassium excretion of 7.5 mmol/day in the presence of severe hypokalemia. These results on urine potassium were atypical for pseudoaldosteronism. Urine sodium excretion was also significantly reduced to 27.5 mmol/day, suggesting low sodium intake due to anorexia. Low sodium intake followed by low sodium delivery to the collecting duct was the crucial cause of decreased urine potassium excretion in pseudoaldosteronism. Clinicians need to understand the side effects of licorice and assess the risks and benefits associated with the use of licorice-containing drugs, especially in patients with risk factors for pseudoaldosteronism, such as advanced age or low body weight. Careful follow-up of blood pressure or serum potassium concentration is required to prevent the development of pseudoaldosteronism.

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival ( P  = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo . Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

Esophageal cancer (EC) is the sixth leading cause of cancer‐related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive a complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA levels in plasma have the potential to be a predictor of response to NAC. In the present study, we focused on miR‐192‐5p, which is highly expressed in EC tissue. The purpose was to investigate the correlations between levels of plasma miR‐192‐5p and the response to NAC. Furthermore, molecular functions of miR‐192‐5p associated with chemosensitivity were examined using EC cell lines. The levels of miR‐192‐5p in plasma before surgery were evaluated in 113 EC patients. Sixty‐nine patients received NAC. miR‐192‐5p levels in the CR group were significantly higher than in the other groups (p = 0.002). The downregulation of miR‐192‐5p in the EC cell line inhibited sensitivity to cisplatin, and the overexpression of miR‐192‐5p in the EC cell line promoted sensitivity to cisplatin. miR‐192‐5p regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR‐192‐5p could be used as a predictor of response to chemotherapy and prognosis in EC patients. Expression of miR‐192 in esophageal cancer regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR‐192 may be used as a predictor of response to chemotherapy in esophageal cancer patients.

Thiamine deficiency can cause various clinical manifestations. Wet beriberi, a phenotype of thiamine deficiency, is often underdiagnosed in clinical practice due to the nonspecificity of symptoms. An 83-year-old man presented to a primary care clinic with a two-month history of progressing edema in the scrotum and lower extremities. The patient reported a weight gain of 10 kg and was treated with diuretics. However, his condition did not improve even after four weeks. The patient was referred to our hospital for further cardiac evaluation. Transthoracic echocardiographic findings were suggestive of a high cardiac output (CO) state, and the thiamine level was decreased. Further medical interview revealed that the patient had a habit of eating two or three large bowls of white rice with a few side dishes for breakfast and dinner. The hemodynamic evaluation revealed high CO and low systemic vascular resistance. The patient's weight decreased from 56.6 to 52.4 kg in the first 2 days after thiamine administration. Six days later, his weight further decreased to 50.8 kg and edema disappeared completely. Clinicians should be aware that excessive consumption of white rice with few side dishes may lead to thiamine deficiency. This case highlights the importance of considering wet beriberi as a cause of excessive edema with high CO state.

Atrial natriuretic peptide (ANP) is a circulating hormone released from the atria in response to wall stretch and volume overload in the setting of heart failure. When atrial fibrillation (AF) becomes long-standing persistent, ANP secretion in response to volume overload is impaired due to degenerative changes of the atria. Here, we report a case of heart failure with preserved ejection fraction and impaired ANP secretion due to long-standing AF. N-terminal pro-brain natriuretic peptide (NT-proBNP) level was elevated (269 pg/mL), whereas the increase in ANP level was marginal (46.1 pg/mL), suggesting impaired ANP secretion due to long-standing AF. Valsartan (80 mg/day) was replaced with sacubitril/valsartan (100 mg/day) without changing other medications. Administration of sacubitril/valsartan was effective in improving the patient's symptoms, such as dyspnea and edema, and reducing NT-proBNP level by increasing endogenous ANP level from 46.1 pg/mL to 117 pg/mL in the first four weeks. This case highlights the possibility of impaired ANP secretion in response to volume overload as a predictor of the diuretic effect of sacubitril/valsartan in heart failure. This may lead to individualized treatment for each patient with heart failure based on natriuretic peptide profiles.

Regional wall motion abnormality in the left ventricular (LV) apex detected on transthoracic echocardiography is commonly interpreted as the presence of a distal left anterior descending (LAD) artery lesion in clinical practice. Herein, we reported a rare case of apical acute myocardial infarction (AMI) caused by an occluded posterior descending branch of the right coronary artery (RCA), in which the correspondence between coronary arterial anatomy and supplied LV apex was evaluated by multi-imaging modalities. Despite the presence of regional wall motion abnormality in the LV apex, left coronary angiography showed no significant coronary artery diseases. It was of note that LAD terminated before the LV apex. Right coronary angiography showed total occlusion of the posterior descending branch. Cardiac computed tomography (CT) clearly demonstrated that the spontaneously recanalized posterior descending branch extended toward the LV apex. Cardiac magnetic resonance imaging (MRI) clearly revealed regional wall motion abnormality corresponding to myocardial edema in the LV apex. Cardiac CT and MRI were powerful tools in clarifying the correspondence between coronary arterial anatomy and supplied LV apex. Clinicians should be aware that localized apical AMI can occur under the condition of occluded posterior descending branch of RCA concomitant with short LAD.