ER, PgR, Ki67, p27Kip1, and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab

Patient and tumor characteristics at baseline. (PDF 6 kb

Lack of effect of bone marrow transplantation on airway hyperresponsiveness in an asthmatic

ABSTRACTBronchial asthma has been recognized as an inflammatory disorder in this past decade. This leads to an assumption that perfect control of inflammatory cells may cure this disease. However, herein we report on an asthmatic whose airway hyperresponsiveness (AHR) did not change after bone marrow transplantation (BMT). The concentrations of acetylcholine to produce a 20% fall in forced expiratory volume in 1 s 15 days before and 98 days after BMT were 900 and 480 μg/mL, respectively. Asthma treatment with beclo-methasone dipropionate and theophylline was continued before and after BMT and a conventional supporting therapy for BMT with cyclosporine A and methylprednisolone, followed by oral administration of tacrolimus hydrate alone inhibited graft-versus-host disease. Plasma interleukin (IL)-4, IL-5 and IgE, but not interferon-γ, levels decreased after BMT. Note that the second measurement of airway sensitivity was performed under systemic administration of tacrolimus. The presented case suggests that replacement of bone marrow-derived inflammatory cells is not enough to reverse once-established AHR. Hence, AHR and airway inflammation may develop independently in some part, but both need to be present for asthma to be present in this asthmatic

Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer

<p>Abstract</p> <p>Background</p> <p>Lymphovascular invasion (LVI) and lymph node metastasis are conventional pathological factors associated with an unfavorable prognosis of urothelial carcinoma of the upper urinary tract (UC-UUT), but little is known about the molecular mechanisms underlying LVI and nodal metastasis in this disease. Rac1 small GTPase (Rac1) is essential for tumor metastasis. Activated GTP-bound Rac1 (Rac1 activity) plays a key role in activating downstream effectors known as Pak (21-activated kinase), which are key regulators of cytoskeletal remolding, cell motility, and cell proliferation, and thus have a role in both carcinogenesis and tumor invasion.</p> <p>Methods</p> <p>We analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained from the surgical specimens of 108 Japanese patients with UC-UUT.</p> <p>Results</p> <p>Rac1 activity and Pak1 protein levels were higher in tumor tissue and metastatic lymph node tissue than in non-tumor tissue (both <it>P </it>< 0.0001). A high level of Rac1 activity and Pak1 protein expression in the primary tumor was related to poor differentiation (<it>P </it>< 0.05), muscle invasion (<it>P </it>< 0.01), LVI (<it>P </it>< 0.0001), and lymph node metastasis (<it>P </it>< 0.0001). Kaplan-Meier survival analysis showed that an increase of Rac1 activity and Pak1 protein was associated with a shorter disease-free survival time (<it>P </it>< 0.01) and shorter overall survival (<it>P </it>< 0.001). Cox proportional hazards analysis revealed that high Rac1 activity, Pak1 protein expression and LVI were independent prognostic factors for shorter overall and disease-free survival times (<it>P </it>< 0.01) on univariate analysis, although only Pak1 and LVI had an influence (<it>P </it>< 0.05) according to multivariate analysis.</p> <p>Conclusions</p> <p>These findings suggest that Rac1 activity and Pak1 are involved in LVI and lymph node metastasis of UC-UUT, and may be prognostic markers for this disease.</p

Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer

L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationships between LAT1 expression and patient outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed. Human epidermal growth factor receptor 2 (HER2)-positive patients with metastasis received trastuzumab therapy. The density of tumor-infiltrating lymphocytes (TILs) was evaluated according to the International Working Group guidelines. In the current study, high LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased TILs, and programmed death ligand 1 positivity. Among the ER-positive and HER2-negative patients, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI 1.35–8.52; p = 0.0094). In conclusion, high LAT1 expression could be used to identify a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer

Protein Profiling of Blood Samples from Patients with Hereditary Leiomyomatosis and Renal Cell Cancer by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an extremely rare syndrome with autosomal dominant inheritance. HLRCC is characterized by a predisposition to leiomyomas of the skin and the uterus as well as renal cell carcinoma. The disease-related gene has been identified as fumarate hydratase (fumarase, FH), which encodes an enzyme involved in the mitochondrial tricarboxylic acid cycle. Protein profiling may give some insight into the molecular pathways of HLRCC. Therefore, we performed protein profiling of blood samples from HLRCC patients, their family members, and healthy volunteers, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) coupled with IMAC-Cu chips. For hierarchical clustering analysis, we used the 45 peaks that revealed significant differences in single-marker analysis over the range from 1500 to 15,000 m/z. Heat map analysis based on the results of clustering distinguished the HLRCC kindred from non-HLRCC subjects with a sensitivity of 94% and a specificity of 90%. SELDI-TOF MS profiling of blood samples can be applied to identify patients with HLRCC and to assess specific molecular mechanisms involved in this condition