Efficacy and Safety of Dual Paclitaxel and Sirolimus Nanoparticle-Coated Balloon.

We evaluated a novel dual active pharmaceutical ingredient (API) drug-coated balloon (DCB), which consists of a coating of nanoparticles encapsulating low-dose paclitaxel (PTX) in combination with sirolimus in a synergistic ratio. Compared to the PTX DCB, the dual API DCB demonstrated similar inhibition of cell proliferation in vitro but at a significantly lower total drug dose (over 13 times lower than sirolimus nanoparticles). Animal experiments demonstrated that the dual API DCB is more effective in inhibiting intimal cell proliferation with insignificant downstream embolic effects and myocardial damage compared to the PTX DCB.

Nanoparticle-mediated synergistic drug combination for treating bone metastasis.

Bone metastasis at an advanced disease stage is common in most solid tumors and is untreatable. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) in tumor-bone marrow microenvironment drives a vicious cycle of tumor progression and bone resorption. Biodegradable nanoparticles (NPs), designed to localize in the tumor tissue in bone marrow, were evaluated in a prostate cancer model of bone metastasis.

The P387 thrombospondin-4 variant promotes accumulation of macrophages in atherosclerotic lesions.

Thrombospondin-4 (TSP4) is a pro-angiogenic protein that has been implicated in tissue remodeling and local vascular inflammation. TSP4 and, in particular, its SNP variant, P387 TSP4, have been associated with cardiovascular disease. Macrophages are central to initiation and resolution of inflammation and development of atherosclerotic lesions, but the effects of the P387 TSP4 on macrophages remain essentially unknown.

Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages.

Thrombospondin-4 (TSP-4) attracted renewed attention recently as a result of assignment of new functions to this matricellular protein in cardiovascular, muscular, and nervous systems. We have previously reported that TSP-4 promotes local vascular inflammation in a mouse atherosclerosis model. A common variant of TSP-4, P387-TSP-4, was associated with increased cardiovascular disease risk in human population studies.

Synergistic combination treatment to break cross talk between cancer cells and bone cells to inhibit progression of bone metastasis.

Advanced-stage cancers often metastasize to bone, and is the major cause of cancer-related morbidity and mortality. Due to poor biodistribution of intravenously administered anticancer drugs within the bone, chemotherapy is not optimally effective in treating bone metastasis. Additionally, overexpression of receptor activator of nuclear factor κB ligand (RANKL) in the bone microenvironment drives the vicious, destructive cycle of progression of bone metastasis and bone resorption.

Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions.

Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.

IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases.

Breakdown of the blood-brain barrier (BBB) precedes lesion formation in the brains of multiple sclerosis (MS) patients. Since recent data implicate disruption of the small intestinal epithelial barrier (IEB) in the pathogenesis of MS, we hypothesized that the increased permeability of the BBB and IEB are mechanistically linked. Zonulin, a protein produced by small intestine epithelium, can rapidly increase small intestinal permeability.

Nucleus accumbens-1/GADD45GIP1 axis mediates cisplatin resistance through cellular senescence in ovarian cancer.

Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the bric-a-brac-tramtrack-broad complex/pox virus and zinc finger gene family, is known to serve important roles in the proliferation and growth of tumor cells, and in chemotherapy resistance. However, the underlying molecular mechanisms through which NAC1 contributes to drug resistance remain unclear. In the present study, the role of NAC1 in drug resistance in ovarian cancer was investigated.

CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review.

KRAS and MAPK1 gene amplification in type II ovarian carcinomas.

In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2%) and 5 (7.

A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies.

Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens.

Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer.

Objective: In the current study we investigated the clinicopathological significance of fatty acid synthase (FASN) expression and its relationship with estrogen receptor (ER) and progesterone receptor (PR) in endometrioid endometrial cancer.

Methods: FASN expression in endometrioid endometrial cancer was assessed by immunohistochemistry using 108 paraffin-embedded tissue specimens and clinical data collected from a retrospective chart review. The specific FASN inhibitor C75 was used to analyze the relationship between FASN expression and cell growth as well as ER/PR expression in endometrioid endometrial cancer cell lines.

PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes.

Somatic mutations in PPP2R1A, which encodes a scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have recently been described in different types of gynecological neoplasias. To extend this observation, we examined the frequency of PPP2R1A mutation in some major histological subtypes of type I and type II ovarian carcinoma. Mutational analysis of PPP2R1A (exons 5 and 6) was performed on 88 primary ovarian carcinomas, including mucinous, clear cell, high-grade serous, and high-grade endometrioid ovarian carcinoma.

Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy?

Objective: This study examined the prognostic significance of copper-transporting P-type adenosine triphosphatase (ATP7B) expression in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy.

Methods: Expression of ATP7B in ovarian carcinoma was assessed by immunohistochemistry and clinical data collected by retrospective review of medical charts.

Results: Overexpression of ATP7B was identified in 25 (29.

Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer.

This study examined the clinical significance of Notch3 expression and assessed its usefulness as a potential therapeutic target in chemoresistant ovarian cancer. Notch3 expression was assessed with immunohistochemical examination, and clinical variables were collected with a retrospective chart review. Notch3 siRNA or γ-secretase inhibitor was used to assess Notch3 function in ovarian cancer cell lines.

NAC1, a BTB/POZ protein overexpressed in uterine sarcomas.

Background: The purpose of this study was to investigate the role of Nucleus accumbens-associated 1 (NAC1) in the development of uterine sarcomas.

Materials And Methods: NAC1 expression and localization in the normal myometrium, benign leiomyoma, and uterine sarcoma were assessed with immunohistochemistry. NAC1-specific siRNA was used to inactivate NAC1 for in vitro biological assays.

Clinicopathologic analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer.

Loss of the AT-rich interactive domain 1A (a putative tumor suppressor) protein BAF250a has recently been described as a frequent event in endometrial carcinoma. In this study, we determined the significance of the loss of AT-rich interactive domain 1A immunoreactivity for several clinicopathologic features of uterine endometrioid carcinoma. AT-rich interactive domain 1A expression was assessed by immunohistochemistry using 111 paraffin-embedded tissue specimens and clinical data collected by a retrospective medical record review.

Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma.

Background: Recently we reported that amplification of the Zinc Finger Protein 217 (ZNF217) gene adversely affects survival of patients with ovarian clear cell carcinoma. This study sought to determine the mechanism by which ZNF217 amplification affects patient survival.

Materials And Methods: Fluorescence in situ hybridization (FISH) was used to detect ZNF217 gene amplification status and ZNF217-specific siRNA was used to inactivate ZNF217 for in vitro biological analyses.

Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma.

Somatic mutations of PIK3CA (phosphoinositide-3-kinase) have recently been shown playing an important role in the pathogenesis of ovarian clear cell carcinoma. In this study, the frequency of PIK3CA mutations and the relationship of PIK3CA mutations with clinicopathologic and biological variables were investigated in ovarian clear cell carcinomas from Japanese patients. Mutational analysis of PIK3CA was performed in 56 primary ovarian clear cell carcinomas from Japanese women.

Sister Mary Joseph's nodule associated with rare endometrial squamous cell carcinoma.

Background: Umbilical metastasis (Sister Mary Joseph's nodule) is a rare physical sign seen only in 1-3 % of patients with an intra-abdominal and/or pelvic malignancy. Here, we present a case of Sister Mary Joseph's (SMJN) nodule originating from a primary squamous cell carcinoma of the endometrium, a rare histological subtype.

Case History: SMJN was detected in a 30-year-old woman after a preoperative CT scan for a suspected umbilical hernia.

[A case of stage IVb cervical carcinoma in which survival was prolonged by two different chemotherapies and CCRT].

Pulmonary metastasis from primary cervical carcinoma is rare, with an incidence of 4.16-7.7%.

Uterine leiomyosarcoma producing granulocyte colony stimulating factor.

Uterine leiomyosarcoma associated with the paraneoplastic production of granulocyte-colony stimulating factor (GCSF) is extremely rare. No case has been reported to date in the English literature. We describe a case of a 56-year-old female with recurrent uterin leiomyosarcoma, associated with leukocytosis (19100/mm) and an elevated serum GCSF (33.

Frequent loss of tumor suppressor ARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of the uterine cervix.

Objectives: Expression of ARID1A (the adenine, thymine-rich interactive domain 1A), a putative tumor suppressor, has recently been shown to be lost in several tumor types. This study investigated whether ARID1A expression was also lost in cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.

Methods: A total of 91 patients with cervical carcinoma were enrolled.

Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma.

Background: The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC).

Methods: ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines.