Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.     

Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.     

Skin tumor initiating activity of therapeutic crude coal tar as compared to other polycyclic aromatic hydrocarbons in SENCAR mice

Crude coal tar (CCT), a complex mixture rich in polycyclic aromatic hydrocarbons (PAHs) including carcinogens such as benzo[a]pyrene (BP), is widely used therapeutically in dermatological practice, particularly in combination with ultraviolet radiation in the treatment of chronic dermatoses such as psoriasis. In this study we analyzed the tumor initiating activity of therapeutic CCT preparation (USP) in a two-stage model system (initiation and promotion) in SENCAR mice. The tumorigenicity of CCT was compared with other conventionally studied carcinogenic PAHs; 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (MCA), benzo[a]pyrene 7,8-diol (BP-7,8-diol) and benzo[a]pyrene (BP). A single topical application of an initiating dose of CCT (20 microliter), DMBA (39 nmol), MCA (746 nmol), BP-7,8-diol (352 nmol) or BP (396 nmol) was followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate (TPA) (3.24 nmol). The first tumor appearance in the CCT treated group was at 6 weeks on test as compared with DMBA and MCA (3 weeks) and BP-7,8-diol and BP (4-5 weeks). In a total of 20 animals after 8 weeks on test the DMBA, MCA, BP-7,8-diol, BP and CCT groups of mice showed 457, 176, 106, 76 and 46 tumors, respectively. After 11 weeks 100% of the mice in each experimental group had developed tumors and the number of tumors/mouse was 24.3, 15.0 9.8, 6.6 and 3.3 in the DMBA, MCA, BP-7,8-diol, BP and CCT groups, respectively. These studies provide first evidence that a single topical application of a therapeutic preparation of CCT possesses skin tumor initiating activity.     

Benzo(a)pyrene diol epoxide-I-DNA adduct formation in the epidermis and lung of SENCAR mice following topical application of crude coal tar

The levels of benzo[a]pyrene diol epoxide-I-deoxyguanosine (BPDE-I-dG) adduct formation in epidermis and lung of SENCAR mice following the topical application of benzo[a]pyrene (BP) alone, crude coal tar (CCT) alone, and the two combined were determined in an enzyme linked immunosorbent (ELISA) assay using monoclonal antibodies. Topical application of two doses of BP (20 micrograms) at 72-h intervals, with sacrifice 24 h later resulted in the formation of 197 fmol and 205 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Topical application of 0.5 ml CCT alone resulted in the formation of 278 fmol and 410 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Simultaneous topical application of 20 micrograms BP and CCT (0.1-0.5 ml) resulted in substantially lower BPDE-I-dG adducts in the epidermis as well as in the lung. Our results suggest that CCT may contain inhibitors of carcinogen-DNA adduct formation and that topical application of CCT produces greater effects on DNA-adduct formation in lung than in epidermis. Thus the cancer-causing potency of the polycyclic aromatic hydrocarbons (PAHs) in CCT may be reduced by other anticarcinogenic constituents present in CCT and systemic absorption of carcinogenic PAHs in CCT applied to skin might have tumorigenic effects in other tissues.     

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage

Introduction

In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage.

Role of 3D sonohysterography in the investigation of uterine synechiae/asherman's syndrome: Pictorial assay

Several imaging methods have been applied for evaluation of suspected uterine synechiae; however, sonohysterography is yet recognised as a valid and accurate modality. Performing three‐dimensional (3D) imaging along with sonohysterography enables evaluation of the uterus in the coronal plane to detect and grade the adhesions that characterise this condition. Thus, 3D sonohysterography is a minimally invasive and cost‐effective tool for investigating suspected synechiae and is particularly useful when the transvaginal sonography findings are normal.     

Spontaneous xenogeneic GvHD in Wilms' tumor Patient‐Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg‐Prkdc ^scid Il2rg ^tm1Sug (NOG) mice are among the ideal animal recipients for generation of human cancer models. Transplantation of human solid tumors having abundant tumor‐infiltrating lymphocytes (TILs) can induce xenogeneic graft‐versus‐host disease (xGvHD) following engraftment and expansion of the TILs inside the animal body. Wilms'' tumor (WT) has not been recognized as a lymphocyte‐predominant tumor. However, 3 consecutive generations of NOG mice bearing WT patient‐derived xenografts (PDX) xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention. In the initial generation, dermatitis, auto‐amputation of digits, weight loss, lymphadenopathy, hepatitis, and interstitial pneumonitis were observed. Despite antibiotic treatment, no response was noticed, and thus the animals were prematurely euthanized (day 47 posttransplantation). Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti‐human CD3 and CD8 antibodies in the xenografts and primary tumor, whereas no microbial infection or lymphoproliferative disorder was found. Mice of the next generation that lived longer (91 days) developed sclerotic skin changes and more severe pneumonitis. Cutaneous symptoms were milder in the last generation. The xenografts of the last 2 generations also contained TILs, and lacked lymphoproliferative transformation. The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD. While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts, this report for the first time documented serial xGvHD in consecutive passages of WT PDX‐bearing models and discussed potential solutions to prevent such an undesired complication.     

Effect of the Source-to-Substrate Distance on Structural,Optoelectronic, and Thermoelectric Properties of Zinc Sulfide Thin Films

Zinc sulfide (ZnS) thin films with variable structural, optical, electrical, and thermoelectric properties were obtained by changing the source-to-substrate (SSD) distance in the physical-vapor-thermal-coating (PVTC) system. The films crystallized into a zinc-blende cubic structure with (111) preferred orientation. The films had a wide 3.54 eV optical band gap. High-quality homogenous thin films were obtained at 60 mm SSD. The sheet resistance and resistivity of the films decreased from 10¹¹ to 10¹⁰ Ω/Sq. and from 10⁶ to 10⁵ Ω-cm, when SSD was increased from 20 mm to 60 mm, respectively. The phase and band gap were also verified by first principles that were in agreement with the experimental results. Thermoelectric characteristics were studied by using the semi-classical Boltzmann transport theory. The high quality, wide band gap, and reduced electrical resistance make ZnS a suitable candidate for the window layer in solar cells.     

Liposome System for Encapsulation of Spirulina platensis Protein Hydrolysates: Controlled-Release in Simulated Gastrointestinal Conditions,Structural and Functional Properties

This study aimed to evaluate the physicochemical, structural, antioxidant and antibacterial properties of chitosan-coated (0.5 and 1% CH) nanoliposomes containing hydrolyzed protein of Spirulina platensis and its stability in simulated gastric and intestine fluids. The chitosan coating of nanoliposomes containing Spirulina platensis hydrolyzed proteins increased their size and zeta potential. The fourier transform infrared spectroscopy (FT-IR) test showed an effective interaction between the hydrolyzed protein, the nanoliposome, and the chitosan coating. Increasing the concentration of hydrolyzed protein and the percentage of chitosan coating neutralized the decreasing effect of microencapsulation on the antioxidant activity of peptides. Chitosan coating (1%) resulted in improved stability of size, zeta potential, and poly dispersity index (PDI) of nanoliposomes, and lowered the release of the hydrolyzed Spirulina platensis protein from nanoliposomes. Increasing the percentage of chitosan coating neutralized the decrease in antibacterial properties of nanoliposomes containing hydrolyzed proteins. This study showed that 1% chitosan-coated nanoliposomes can protect Spirulina platensis hydrolyzed proteins and maintain their antioxidant and antibacterial activities.     

Evaluating changes in pulse transit time drop index in patients with obstructive sleep apnea before and during CPAP therapy

Airflow limitation in patients with obstructive sleep apnea (OSA) leads to arousal, increased sympathetic nervous system activity, and elevated blood pressure, which causes a decrease in pulse transit time (PTT). The present study aims to evaluate the effect of CPAP therapy on PTT in patients with moderate to severe OSA. This was a cross‐sectional study. Split‐night polysomnography (PSG) study was performed for each participant with apnea‐hypopnea index (AHI) ≥ 15 before and during CPAP therapy. The PTT was calculated as the time interval between the R wave of the electrocardiogram and the following arrival point in fingertip photoplethysmography. PTT drop was defined as a fall in the PTT curve of ≥15 ms lasting at least for 3 s and at most for 30 s. PTT drop index was defined as the number of drops in PTT that occur per hour of sleep. A total of 30 patients were included. PTT significantly increased, and PTT drop index significantly decreased during CPAP therapy (P < 0.001). PTT was significantly correlated to sleep efficiency (r _s = −0.376, P = 0.049) and oxygen desaturation index (ODI) (r _s = −0.428, P = 0.018). PTT drop index was strongly correlated to AHI (r _s = 0.802, P < 0.001), respiratory disturbance index (RDI) (r _s = 0.807, P < 0.001), ODI (r _s = 0.693, P < 0.001), arousal index (r _s = 0.807, P < 0.001), and periodic leg movement (PLM) index (r _s = 0.400, P = 0.035). Overall, the findings from this study indicated that the PTT drop index is a non‐invasive and useful marker for evaluating the severity of OSA and the effectiveness of treatment in patients with moderate to severe OSA.