Increasing roughness of the human breast cancer cell membrane through incorporation of gold nanoparticles.

Gold nanoparticles (AuNPs) have been proposed for use in the treatment of different types of cancer, including breast cancer. At present, neither the mechanisms of AuNP interaction with the plasma membrane surface and their delivery and intracellular distribution in cancer cells nor their effect on the plasma membrane so as to allow cell incorporation of larger amounts of AuNPs is known. The objective of this work was to study the interaction of bare 20 nm diameter AuNPs with the plasma membrane of human MCF-7 breast cancer cells, as well as their uptake, intracellular distribution, and induction of changes on the cell surface roughness. The dynamics of intracellular incorporation and the distribution of AuNPs were observed by confocal laser scanning microscopy. Changes in roughness were monitored in synchronized MCF-7 cells by atomic force microscopy high-resolution imaging at 6 hour intervals for 24 hours during a single cell cycle. The results show that bare AuNPs are capable of emitting fluorescence at 626 nm, without the need for a fluorescent biomarker, which allows monitoring their uptake and intracellular distribution until they reach the nucleus. These results are correlated with changes in cell roughness, which significantly increases at 12 hours of incubation with AuNPs, when compared with control cells. The obtained data provide bases to understand molecular processes of the use of AuNPs in the treatment of different diseases, mainly breast cancer.

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin.

Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1­ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1­deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild­type MDA-MB-231 cells, to demonstrate its effects as a chemo­ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo­ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo­ or radiosensitizing agent regardless of the BRCA1 status in breast cancer.

Knowledge of Pap screening and human papillomavirus among women attending clinics in Medellín, Colombia.

This study evaluated Pap screening and human papillomavirus (HPV) knowledge in a population of Colombian women as a possible contributing factor of low cervical cancer screening success. This is a descriptive, cross-sectional analysis of 454 women who were approached in five different hospitals and clinics throughout Medellín, Colombia. Of them, 449 females agreed to participate and answered a standardized face-to-face questionnaire regarding Pap screening and HPV knowledge. Using logistic regression, predictors of both Pap and HPV knowledge were examined. Overall, 76.3% of the participants exhibited a high level of Pap screening knowledge, while only 7.8% showed high level of HPV knowledge. Of the 449 women, 71.5% reported that it had been 1 year or less since their last Pap test, while 7.8% reported never having had a Pap test or not having had a recent test. Factors influencing Pap screening knowledge included education level and insurance; factors influencing HPV knowledge included education level and age. The high level of Pap screening knowledge and use do not explain the high cervical cancer rates in Colombia. The results of this study suggest that educational efforts should be focused on increasing women's knowledge and awareness of HPV in anticipation of the availability of HPV vaccines and HPV tests for screening.

Efficacy of concomitant chemoradiation and surgical salvage for N3 nodal disease associated with upper aerodigestive tract carcinoma.

OBJECTIVES/HYPOTHESIS: To determine whether an aggressive approach using trimodality therapy would improve the outcome in head and neck cancer patients with advanced (N3) nodal disease. STUDY DESIGN: In this retrospective, nonrandomized review, we analyzed a subset of patients who were treated in a targeted chemoradiation therapy protocol, consisting of 31 patients who received treatment between June 1993 and June 1997. METHODS: Patients received selective intra-arterial infusions of cisplatin (150 mg/m2/wk for 4 weeks) and concomitant radiation therapy (2 Gy/fraction x 35 daily fractions over a 7-wk period) to the primary and clinically positive nodal disease. The patients were re-evaluated 2 months later and underwent salvage neck dissections if there was any residual disease. RESULTS: Classification of disease in the primary site was as follows: T1 in 2 patients, T2 in 6 patients, T3 in 14 patients, and T4 in 9 patients. Among the 31 patients who were assessed for response at the nodal site, 4 of 31 (13%) had a complete response, 21 of 31 (68%) had a partial response, and 1 of 31 (3%) had no response. Excluding the 5 patients who could not be evaluated, 4 of 26 patients (15%) had a complete response, 21 of 26 (81%) had a partial response, and 1 of 26 (4%) had no response. Nineteen patients subsequently underwent neck dissection, and five patients had histological evidence of residual disease. The remaining seven patients included four who had a complete response in their necks and three who died of intercurrent disease before re-staging. Among the 23 patients who were rendered disease free, there were no recurrences within the neck, whereas 1 patient had recurrence at the primary site and 11 patients had recurrence at distant sites. With a median follow-up of 15 months (range, 4-41 mo), the 3-year overall survival and disease-specific survival were 41% and 43%, respectively. CONCLUSIONS: Targeted chemoradiation therapy followed by surgical salvage is a highly effective approach for regional control of patients with N3 nodal disease, whereas additional strategies are required to address the problem of distant metastases.

Antibody response to Klebsiella pneumoniae 60 kDa protein in familial and sporadic ankylosing spondylitis: role of HLA-B27 and characterization as a GroEL-like protein.

OBJECTIVE: To study the antibody response of HLA-B27+ patients with ankylosing spondylitis (AS) and their first degree relatives to the 60 kDa protein of Klebsiella pneumoniae and to characterize this protein. METHODS: Sera from 84 individuals were analyzed by ELISA to determine the titer of antibodies against the 60 kDa protein of K. pneumoniae. Subjects were divided into 3 categories: Group 1: 44 HLA-B27+ AS related individuals (35 patients, 9 healthy controls); Group 2: 28 healthy B27- AS related individuals; and Group 3: 12 healthy B27- non-AS related subjects. The 60 kDa protein of K. pneumoniae was induced at 45 degrees C and purified by electroelution from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was characterized as a GroEL-like heat shock protein (HSP). The recognition of GroEL-like protein was confirmed by immunoblot of 2 dimension electrophoresis. The response to GroEL-like protein from other bacteria and the response to lipopolysaccharide (LPS) was also analyzed by immunoblot. RESULTS: HLA-B27+ individuals (Group 1), independent of their disease status, showed a significant higher response to the 60 kDa protein of K. pneumoniae than HLA-B27- subjects from Groups 2 and 3 (p < 0.0001). This protein was characterized as a HSP of the GroEL family and designated HSP60Kp. The GroEL of other enterobacteria as well as that of Mycobacterium leprae were recognized by HLA-B27+ individuals by immunoblot, whereas HLA-B27- individuals did not. LPS was not recognized by HLA-B27 positive or negative subjects. CONCLUSION: These findings suggest a relationship between HLA-B27 and the response to a GroEL-like protein that could have implications in AS.

The relationship between frontal sinus drainage and osteomeatal complex disease: a CT study in 217 patients.

Over a period of 2 years we reviewed the CT scans of 217 patients with recurrent sinusitis. Our findings revealed a number of cases of osteomeatal complex disease with no frontal sinus involvement. This result is difficult to reconcile with the concept of a common drainage in the middle meatus shared by the frontal and anterior ethmoid sinuses. We conclude that the frontal sinus drains separately from the other paranasal sinuses in a large percentage of cases, and that the frontal sinus is frequently spared when there is ethmoid or maxillary sinusitis.

Unilateral absence of ventilation and perfusion due to thoracic aortic aneurysm.

An elderly man presented with progressive atelectasis of the left lung, a mediastinal mass, and dilatation of the thoracic aorta. Ventilation and perfusion radionuclide lung scans revealed the complete absence of ventilation in the left lung and near-complete absence of perfusion. Evaluation by MRI and angiography showed an obstructing mediastinal "mass" to be a saccular aortic aneurysm. A thoracic aortic aneurysm should be a consideration in the differential diagnosis for unilateral decrease or absence of ventilation and perfusion with a history or findings of mediastinal mass or aneurysm.

Pleural aspergillosis diagnosed by computerized tomography.

As shown by the case we have reported, patients with a chronic pneumothorax and nodular, thickened pleura may have pleural aspergillosis. We recommend that when such patients have CT of the chest, the examiner use the alternate dependent position to look for mobile pleural debris.

Extramedullary plasmacytoma of the thyroid.

We report a patient with solitary extramedullary plasmacytoma of the thyroid gland. We describe the computed tomographic findings correlated with the radionuclide imaging and surgical findings and review the related literature.

Intrarenal rupture of the abdominal aorta: CT features.

Computed tomography in patients with a ruptured abdominal aortic aneurysm usually demonstrates the aneurysm with blood in the posterior para- and perirenal spaces. Hemorrhage into the adjacent perirenal space occurs because the aorta, via the renal vascular pedicle, is in continuum with this compartment. The kidney is commonly displaced but not compromised functionally. We report a case of an asymptomatic chronic intrarenal rupture of a focal aortic aneurysm that presented as a mass in a nonfunctioning kidney.

Bone marrow expansion of the thyroid cartilage: a source of confusion with malignant invasion in CT studies.

A patient with asymmetrical widening of the thyroid cartilage with decreased ossification of the inner thyroid lamina simulating tumor invasion on CT is described. Histologically, no tumor was identified. A review of the pertinent literature and implications are discussed.

Stabilization of biliary drainage catheters.

Accidental pulling-out of internal biliary catheters can still occur despite adequate fixation at the skin. We have combined the non-suture method with catheter molding in an attempt to prevent dislodgement of the catheter.

Intrahepatic aneurysm: a rare cause of segmental biliary obstruction.

We report a patient with an intrahepatic artery aneurysm causing segmental biliary obstruction. The patient, a 64-year-old man, had persistent elevation of alkaline phosphatase which led to investigation and diagnosis.