A clinical evaluation of an organ culture system to predict patient response to cancer therapy.

Introduction: organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy.

Methods: A multicenter, prospective, single-arm observational trial.

The human tumor microbiome is composed of tumor type-specific intracellular bacteria.

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome.

Primary Coenzyme Q deficiency Due to Novel ADCK3 Variants, Studies in Fibroblasts and Review of Literature.

Primary deficiency of coenzyme Q10 (CoQ10 ubiquinone), is classified as a mitochondrial respiratory chain disorder with phenotypic variability. The clinical manifestation may involve one or multiple tissue with variable severity and presentation may range from infancy to late onset. ADCK3 gene mutations are responsible for the most frequent form of hereditary CoQ10 deficiency (Q10 deficiency-4 OMIM #612016) which is mainly associated with autosomal recessive spinocerebellar ataxia (ARCA2, SCAR9).

The Clinical Significance of HPV Type in Women with Recurrent Cytological Atypia.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected.

Trends and Patterns of Concealed Handgun License Applications: A Multistate Analysis.

Recent waves of legislation have made it much easier for gun owners to obtain a Concealed Handgun License (CHL) and thereby carry their guns in public except when explicitly prohibited. Because data are difficult to access, our understanding of who seeks and obtains such licenses remains limited. Using data obtained through Freedom of Information Act requests, this article fills this empirical gap by describing demographic trends and characteristics of applicants for CHLs in five states: Florida, Indiana, Massachusetts, Texas, and Utah.

Recent trends of cervical cancer and Cervical Intraepithelial Neoplasia 3 (CIN3) in Israel.

Purpose: This study describes time trends of cervical cancer and Cervical Intraepithelial Neoplasia 3 (CIN3) in Israel in the years 1986-2010 and characterizes these patients by demographics.

Methods: A retrospective survey based on cervical cancer and CIN3 data documented in the computerized system of the second largest Health Maintenance Organizations (HMO) in Israel, "Maccabi Healthcare Services" (MHS) between 1986 and 2010.

Results: 737 cervical cancer patients and 3,459 patients of CIN3 were reported between 1986 and 2010.

Prevalence and correlates of human papillomavirus genotypes among patients with cervical cancer and cervical intraepithelial neoplasia 3 in Israel.

Objectives: This study aimed to assess the prevalence of human papillomavirus (HPV) in Israeli patients with cervical cancer and cervical intraepithelial neoplasia 3 (CIN3), to describe the distribution of the virus genotypes among positive cases, to characterize patients positive to HPV and, in particular, patients positive to HPV-16 and/or -18, and to evaluate the possible contribution of implementing HPV vaccination in Israel.

Methods: Samples from 84 patients with cervical cancer and 886 patients with CIN3, archived at the Maccabi Institute of Pathology, were screened for HPV. DNA extraction was performed using DNeasy Blood and Tissue Kit/QIAGEN.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

Background: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers.

Objectives: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011.

PAR-3 knockdown enhances adhesion rate of PANC-1 cells via increased expression of integrinαv and E-cadherin.

The balance between the adhesion of cancer cells to extracellular matrix and their migratory potential, as well as their proteolytic activity, are important parameters that determine cancer cells invasiveness and metastasis. Since thrombin has been implicated in cancer progression, we studied the role(s) of thrombin-activated receptors in the adhesion process. We stably knocked down proteinase-activated receptors (PARs) -1, or -3 in human pancreatic adenocarcinoma PANC-1 cells.

Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic epithelial cell clusters.

We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera.

Cervical Pap screening among Israeli women, 2005-2010.

Purpose: This study describes the distribution and the trends of cervical abnormalities in Israel, based on Pap smear results.

Methods: A retrospective analysis of cervical smears received by the Central Pathology Laboratory of Maccabi Healthcare Services between January 2005 and December 2010.

Results: In total, 711,541 Pap smears were screened in the study period.

Proteinase-activated receptors differentially modulate in vitro invasion of human pancreatic adenocarcinoma PANC-1 cells in correlation with changes in the expression of CDC42 protein.

Objectives: Proteinase-activated receptor-1 (PAR-1) and PAR-2 have been associated with increased invasiveness and metastasis in human malignancies. The role of PAR-3 has been less investigated. We examined the role of PARs in a human pancreatic adenocarcinoma PANC-1 cell line phenotype in vitro.

The effect of chemotherapy on telomere dynamics: clinical results and possible mechanisms.

Telomeres are the chromosomal end components, and their length in hematopoietic stem cells correlates with the bone marrow proliferative reserve. There are few data regarding telomere dynamics in hematopoietic stem cells after exposure to chemotherapy. We show that the attrition of telomeres after cytotoxic treatment correlates with the intensity of chemotherapy.

Knock-down of plasminogen-activator inhibitor-1 enhances expression of E-cadherin and promotes epithelial differentiation of human pancreatic adenocarcinoma cells.

High levels of plasminogen activator inhibitor-1 (PAI-1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI-1 in human pancreatic adenocarcinoma (PAC) PANC-1 cell line biology, we used anti-PAI-1 shRNA to create stable PAI-1 deficient cells (PD-PANC-1s). PD-PANC-1s exhibited a heterogeneous morphology.

Hypnotizability and sensorimotor gating: a dopaminergic mechanism of hypnosis.

Dopaminergic mechanisms have been theorized to influence hypnotizability and sensorimotor gating. In this study, the authors investigated an association between sensorimotor gating, as measured by prepulse inhibition (PPI), and hypnotizability, as assessed by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). They found an inverse correlation between the SSHS:C and PPI.

Israeli norms for the Stanford hypnotic susceptibility scale, Form C.

A Hebrew version of the 12-item Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) was administered to 169 subjects in Israel. The authors compared the results with those obtained for the English original administered in the USA and with an additional group of 38 English-speaking subjects in Israel, as well as with versions translated into Spanish (2 versions, for Spain and for Mexico), Italian, German, and Dutch. Mean scores and pair-wise rank-order correlations between item pass rates were comparable across the different samples.

Cognitive impairment is prevalent in pseudohypoparathyroidism type Ia, but not in pseudopseudohypoparathyroidism: possible cerebral imprinting of Gsalpha.

Objective: Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disorder characterized by resistance to multiple hormones that work via cAMP such as PTH and TSH, accompanied by typical skeletal features including short stature and brachydactyly, termed Albright hereditary osteodystrophy (AHO). In affected kindreds, some members may have AHO but not hormone resistance; they are termed as pseudopseudohypoparathyroidism (PPHP). The molecular basis for the disorder is heterozygous inactivating mutation of the Gsalpha gene.

Expression of tetraspanins in peripheral blood leukocytes: a comparison between normal and infectious conditions.

The role of tetraspanins is undefined, despite their detection in diverse cell types and functions. This study addresses the characterization of tetraspanin expression levels in normal peripheral blood leukocytes (PBL) and in patients with bacterial infection. Membranal and cytoplasmic expression of CD9, CD53, CD63, CD81, CD82 and CD151 in polymorphonuclears (PMN), monocytes, B and T lymphocytes was assessed using flow cytometry.

Microenvironment factors do not afford myeloma cell lines protection from simvastatin.

Background: The intensive interactions of myeloma cells (multiple myeloma, MM) with microenvironmental components of the bone marrow contribute significantly to their proliferation and survival. It has been shown that these signals confer drug resistance, delineating their circumvention as a primary objective in disease treatment. This study was designed to assess the effect of some major extracellular factors on the previously established anti-neoplastic response of myeloma cells to simvastatin (Sim).

G protein-activated K+ channels: a reporter for rapid activation of G proteins by lysophosphatidic acid in Xenopus oocytes.

Threshold concentrations of lysophosphatidic acid (LPA) or acetylcholine (ACh) induce pertussis toxin (PTX)-sensitive rapid desensitization of responses to LPA in Xenopus oocytes. To demonstrate that threshold [LPA] rapidly activates Gi/o proteins, we used the G protein-activated K+ channel (GIRK) as a reporter. Low [LPA] induced IK+ in <3 s of the agonist addition with little or no activation of chloride current.

Co-administration of simvastatin and cytotoxic drugs is advantageous in myeloma cell lines.

We have evaluated the potential application of simvastatin (Sim) combined with conventional cytotoxic drugs for the treatment of multiple myeloma. RPMI 8226 and U266 myeloma cells seeded in culture plates were treated with Sim (5 and 10 microM, respectively) combined with melphalan (Mel; 25 and 20 microM, respectively) or dexamethasone (Dex; 1 microM). We assessed cell cycle (propidium iodide staining and flow cytometric analysis), cell morphology, viability (WST1), total cell count and cell death (Trypan blue exclusion).

Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures.

Background: Cisplatin (CDDP) dose-limited by its side-effects is, in some instances, synergistically amplified when combined with tamoxifen (TAM). TAM has been shown to modulate apoptotic pathways of normal endometrial cells, whereas CDDP induces apoptosis in malignant endometrial cells. Their combined effect on normal or malignant endometrium is as yet unknown.

Initial exposed phosphatidylserine levels correlate with cellular response to cytotoxic drugs.

Phosphatidylserine's (PS) membranal distribution is associated with an expanding variety of biological processes. We studied the relevance of preliminarily exposed membranal PS levels to cellular effects of cytotoxic agents. PBL of normal controls (n = 18) and patients with doxorubicin-treated breast carcinoma (n = 27) or 5'-fluorouracil-treated colorectal cancer (n = 32) were assayed before and after drug infusion.

Postpartum chills phenomenon: is it a feto-maternal transfusion reaction?

Objective: To examine the theory that the postpartum shivering phenomenon is related to feto-maternal bleed during the third stage of labor.

Methods: One hundred laboring low-risk women who had a normal vaginal delivery were observed for the presence of postpartum chills. The duration of the first and second stages of labor changes in body temperature, maternal and fetal blood types and the use of epidural anesthesia were recorded.