Standard treatment options for breast cancer include surgery, chemotherapy, radiation, and targeted therapies, such as adjuvant hormonal therapy and monoclonal antibodies. Recently, the recognition that chronic inflammation in the tumor microenvironment promotes tumor growth and survival during different stages of breast cancer development has led to the development of novel immunotherapies. Several immunotherapeutic strategies have been studied both preclinically and clinically and already have been shown to enhance the efficacy of conventional treatment modalities. Therefore, therapies targeting the immune system may represent a promising next-generation approach for the treatment of breast cancers. This review will discuss recent findings that elucidate the roles of suppressive immune cells and proinflammatory cytokines and chemokines in the tumor-promoting microenvironment, and the most current immunotherapeutic strategies in breast cancer.

Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men’s death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as androgen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa. In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it eventually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards understanding PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.

Objective: Axenfeld-Rieger syndrome (ARS) is phenotypically and genetically heterogeneous. In this study, we identified the underlying genetic defect in a Chinese family with ARS. Methods: A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 (PITX2) gene and the forkhead box C1 (FOXC1) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results: Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c.198_201delinsTTTCT (p.M66Ifs*133) was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions: We detected a novel frameshift mutation p.M66Ifs*133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been reported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.

Objective: To explore whether there exist differences in cognitive development between singletons and twins born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Methods: A total of 566 children were recruited for the study, including 388 children (singletons, n=175; twins, n=213) born after IVF and 178 children (singletons, n=87; twins, n=91) born after ICSI. The cognitive development was assessed using the Chinese-Wechsler Intelligence Scale for Children (C-WISC). Results: For all pre-term offspring, all the intelligence quotient (IQ) items between singletons and twins showed no significant differences no matter if they were born after IVF or ICSI. There was a significant difference in the cognitive development of IVF-conceived full-term singletons and twins. The twins born after IVF obtained significantly lower scores than the singletons in verbal IQ (containing information, picture & vocabulary, arithmetic, picture completion, comprehension, and language), performance IQ (containing maze, visual analysis, object assembly, and performance), and full scale IQ (P<0.05). The cognitive development of full-term singletons and twins born after ICSI did not show any significant differences. There was no significant difference between the parents of the singletons and twins in their characteristics where data were collected, including the age of the mothers, the current employment status, the educational backgrounds, and areas of residence. There were also no consistent differences in the duration of pregnancy, sex composition of the children, age, and height between singletons and twins at the time of our study although there existed significant differences between the two groups in the sex composition of the full-term children born after ICSI (P<0.05). Conclusions: Compared to the full-term singletons born after IVF, the full-term twins have lower cognitive development. The cognitive development of full-term singletons and twins born after ICSI did not show any significant differences. For all pre-term offspring, singletons and twins born after IVF or ICSI, the results of the cognitive development showed no significant differences.

Our intent is to examine the predictive role of Charlson comorbidity index (CCI) on mortality of patients with type 2 diabetic nephropathy (DN). Based on the CCI score, the severity of comorbidity was categorized into three grades: mild, with CCI scores of 1–2; moderate, with CCI scores of 3–4; and severe, with CCI scores ≥5. Factors influencing mortality and differences between groups stratified by CCI were determined by logistical regression analysis and one-way analysis of variance (ANOVA). The impact of CCI on mortality was assessed by the Kaplan-Meier analysis. A total of 533 patients with type 2 DN were enrolled in this study, all of them had comorbidity (CCI score >1), and 44.7% (238/533) died. The mortality increased with CCI scores: 21.0% (50/238) patients with CCI scores of 1–2, 56.7% (135/238) patients with CCI scores of 3–4, and 22.3% (53/238) patients with CCI scores ≥5. Logistical regression analysis showed that CCI scores, hemoglobin, and serum albumin were the potential predictors of mortality (P<0.05). One-way ANOVA analysis showed that DN patients with higher CCI scores had lower levels of hemoglobulin, higher levels of serum creatinine, and higher mortality rates than those with lower CCI scores. The Kaplan-Meier curves showed that survival time decreased when the CCI scores and mortality rates went up. In conclusion, CCI provides a simple, readily applicable, and valid method for classifying comorbidities and predicting the mortality of type 2 DN. An increased awareness of the potential comorbidities in type 2 DN patients may provide insights into this complicated disease and improve the outcomes by identifying and treating patients earlier and more effectively.

This study is aimed to investigate the clinical significance and the short-term prognostic value of fragmented QRS (fQRS) for patients with acute myocardial infarction (AMI). Three hundred patients with AMI were tested with retrospective analysis on the patients’ clinical information, hospitalized treatment, fQRS onset time, location of lesions, and other relevant data, in order to assess the relationship between the presence of fQRS and its prognosis. The rates of malignant cardiac arrhythmia, left ventricular systolic dysfunction (LVSD), and mortality in the positive fQRS group were 13.6%, 29.2%, and 23.7%, respectively, with all showing a p value <0.05. For the ST segment elevation myocardial infarction (STEMI) subgroup, all the rates showed significant differences with a p value <0.01, while for the non-STEMI (NSTEMI) subgroup showed no significant differences. In patients with a positive fQRS, there were no differences in malignant cardiac arrhythmia between patients with and without percutaneous coronary intervention (PCI) (p>0.05). As for the LVSD and mortality, the p values between patients with and without PCI were 0.031 and 0.000, respectively, suggesting statistical significance. The results imply that AMI patients with positive fQRS especially for the patients with STEMI had higher rates of malignant cardiac arrhythmia, LVSD, and mortality than the non-fQRS group. Patients of AMI with positive fQRS, who underwent early revascularization, could lower the incidence of the cardiovascular event. In addition, the presence of fQRS could be used as an indication of early intervention treatment for patients.

Background: Lung cancer ranks as the fifth largest of all cancer cases in Thailand. However, it is the first leading cancer in the northern part of Thailand (data from 2003–2007). There are several predisposing causes that lead to lung cancer and one important inducement is particulate matters (PMs). Lampang Province in Thailand is famous for the ceramic industry, where there are over 200 ceramic industrial factories. PMs are produced during the ceramic manufacturing process and spread throughout all of the working areas. It is very possible that workers could directly inhale PM-contaminated air during working hours. Objective: This study focuses on the toxic effects of PMs collected from ceramic factories on genes and lungs of rats. Methods: PMs collected from six ceramic factories in Lampang Province were extracted using dimethyl sulfoxide (DMSO). The inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to analyze the chemical elements at lower and higher concentrations, respectively. Then, the toxicity of PMs on the genes was examined by the Ames test, and subsequently, the effect of PMs on DNA was examined by quantifying the amount of 8-hydroxy-2′-deoxyguanosine (8-OHdG). Finally, the toxicity of the PMs on rat’s lungs was examined by histology. Results: As chemical elements of lower concentrations, cadmium, chromium, nickel, copper, and lead were detected by ICP-MS. As chemical elements of higher concentrations, manganese, magnesium, zinc, iron, potassium, calcium, and sodium were detected by ICP-OES. No mutagenicity in Salmonella typhimurium was found in the PM extracts from all six factories by utilizing the Ames test. In the histological study, the reduction in spaces of alveolar ducts and sacs, and terminal bronchioles, the thickening of interstitial connective tissues were noted by PM extracts in high amounts (100 and 350 µg). Female rats were more sensitive to PM extracts than males in terms of their pulmonary damages. Conclusions: PMs were not mutagenic to S. typhimurium but can damage the lung tissue of rats.

Objective: This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing (XNJ). Methods: The rats were divided into two groups, ischemia-reperfusion (IR) and sham-operated (SO) rats. Each group contained two subgroups: pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion (MCAO). The blood samples were collected punctually after oral administration and a specific gas chromatographic system-flame ionization detector (GC-FID) method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results: After administration of borneol, the maximum plasma concentration (C_max) and area under the curve (AUC) values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the C_max and AUC had higher values in the borneol subgroup (P<0.05). Conclusions: These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.

Objective: Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods: Synovial membranes were obtained from 36 patients with knee osteoarthritis (OA) who underwent joint replacement surgery. From this sample, the diagnosis of amyloid was determined by Congo red staining, which demonstrated apple-green birefringence under a polarized microscope. All synovial membranes were immunohistochemically characterized for the expressions of amyloid immunoglobulin light chain (AL-κ and AL-λ), serum amyloid-A (SAA), amyloidogenic transthyretin (ATTR), and amyloidogenic β2-microglobulin (Aβ2M). Matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry (MALDI-TOF MS) was used to analyze transthyretin (TTR) isoforms in the serum of each patient. Results: Nine cases (25%) were found to be amyloid-positive. Immunohistochemically, eight cases (88.9%) had ATTR deposition, and one sample (11.1%) was shown to be AL-κ-positive. MALDI-TOF MS identified that the TTR in the serum of the patients was unmodified wild-type TTR, TTR-Cys-S-S-Cys, and TTR-Cys-S-S-CysGly. The age at surgery and the disease duration were significantly higher in the ATTR-positive group than in the ATTR-negative group. Knee score and function score were significantly lower in the ATTR-positive group than in the ATTR-negative group. Conclusions: Amyloid deposition in synovial membranes of OA patients was found to be ATTR and AL-κ. TTR in the serum of the patients was unmodified wild-type TTR together with two isoforms. The high age at surgery, long disease duration, and a deteriorated knee function were associated with ATTR amyloid deposition in the osteoarthritic knee joints.

In this study, we investigated the molecular phylogeny of 64 clinical isolates which were identified as Sporothrix schenckii sensu lato by morphological identification. All of the strains were isolates from patients from several provinces in China. The phylogeny was inferred by DNA sequence analyses based on datasets of the ribosomal internal transcribed spacer (ITS) and a combined ITS and partial β-tubulin region. Reference sequences were retrieved from GenBank. Results showed that all of the isolates were clustered in a distinct clade with a type of Sporothrix globosa. Our analysis showed that S. globosa is the causal agent of the tested sporotrichosis in China, rather than S. schenckii that was generally believed to be the case. The existence of S. schenckii in China remains to be confirmed. This study improved our understanding of the distribution of the species in S. schenckii complex.