bluuebunny/crossref_metadata_2025 huggingface dataset:
NUCKS overexpression in breast cancer
Authors: Drosos Yiannis , Kouloukoussa Mirsini , Østvold Anne Carine , Grundt Kirsten , Goutas Nikos , Vlachodimitropoulos Dimitrios , Havaki Sophia , Kollia Panagoula , Kittas Christos , Marinos Evangelos , Aleporou-Marinou Vassiliki
Published: August 2009

Background

NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR), real-time PCR (qRT-PCR) and Western immunoblot analyses in the primary cell cultures developed from the same biopsies.

Results

The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS). It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures.

Conclusion

The results show overexpression of the NUCKS protein in a number of non malignant breast lesions and cancerous tissues. In particular, the NUCKS overexpression in ADH and DCIS indicates a significant role of this protein in neoplastic progression.
Community response to intermittent preventive treatment of malaria in infants (IPTi) delivered through the expanded programme of immunization in five African settings
Authors: Gysels Marjolein , Pell Christopher , Mathanga Don P , Adongo Philip , Odhiambo Frank , Gosling Roly , Akweongo Patricia , Mwangi Rose , Okello George , Mangesho Peter , Slutsker Lawrence , Kremsner Peter G , Grobusch Martin P , Hamel Mary J , Newman Robert D , Pool Robert
Published: August 2009

Background

IPTi delivered through EPI has been shown to reduce the incidence of clinical malaria by 20–59%. However, new health interventions can only be effective if they are also socially and culturally acceptable. It is also crucial to ensure that attitudes to IPTi do not negatively influence attitudes to and uptake of immunization, or that people do not misunderstand IPTi as immunization against malaria and neglect other preventive measures or delay treatment seeking.

Methods

These issues were studied in five African countries in the context of clinical trials and implementation studies of IPTi. Mixed methods were used, including structured questionnaires (1,296), semi-structured interviews (168), in-depth interviews (748) and focus group discussions (95) with mothers, fathers, health workers, community members, opinion leaders, and traditional healers. Participant observation was also carried out in the clinics.

Results

IPTi was widely acceptable because it resonated with existing traditional preventive practices and a general concern about infant health and good motherhood. It also fit neatly within already widely accepted routine vaccination. Acceptance and adherence were further facilitated by the hierarchical relationship between health staff and mothers and by the fact that clinic attendance had a social function for women beyond acquiring health care. Type of drug and regimen were important, with newer drugs being seen as more effective, but potentially also more dangerous. Single dose infant formulations delivered in the clinic seem to be the most likely to be both acceptable and adhered to. There was little evidence that IPTi per se had a negative impact on attitudes to EPI or that it had any affect on EPI adherence. There was also little evidence of IPTi having a negative impact on health seeking for infants with febrile illness or existing preventive practices.

Conclusion

IPTi is generally acceptable across a wide range of settings in Africa and involving different drugs and regimens, though there is a strong preference for a single dose infant formulation. IPTi does not appear to have any negative effect on attitudes to EPI, and it is not interpreted as immunization against malaria.
Incidental thyroid lesions detected by FDG-PET/CT: prevalence and risk of thyroid cancer
Authors: Bae Ja Seong , Chae Byung Joo , Park Woo Chan , Kim Jeong Soo , Kim Sung Hoon , Jung Sang Seol , Song Byung Joo
Published: August 2009

Background

Incidentally found thyroid lesions are frequently detected in patients undergoing FDG-PET/CT. The aim of this study was to investigate the prevalence of incidentally found thyroid lesions in patients undergoing FDG-PET/CT and determine the risk for thyroid cancer.

Methods

FDG-PET/CT was performed on 3,379 patients for evaluation of suspected or known cancer or cancer screening without any history of thyroid cancer between November 2003 and December 2005. Medical records related to the FDG-PET/CT findings including maximum SUV(SUVmax) and pattern of FDG uptake, US findings, FNA, histopathology received by operation were reviewed retrospectively.

Results

Two hundred eighty five patients (8.4%) were identified to have FDG uptake on FDG-PET/CT. 99 patients with focal or diffuse FDG uptake underwent further evaluation. The cancer risk of incidentally found thyroid lesions on FDG-PET/CT was 23.2% (22/99) and the cancer risks associated with focal and diffuse FDG uptake were 30.9% and 6.4%. There was a significant difference in the SUVmax between the benign and malignant nodules (3.35 ± 1.69 vs. 6.64 ± 4.12; P < 0.001). There was a significant correlation between the SUVmax and the size of the cancer.

Conclusion

The results of this study suggest that incidentally found thyroid lesions by FDG-PET/CT, especially a focal FDG uptake and a high SUV, have a high risk of thyroid malignancy. Further diagnostic work-up is needed in these cases.
Computerized surveillance of opioid-related adverse drug events in perioperative care: a cross-sectional study
Authors: Eckstrand Julie A , Habib Ashraf S , Williamson Abbie , Horvath Monica M , Gattis Katherine G , Cozart Heidi , Ferranti Jeffrey
Published: August 2009

Background

Given the complexity of surgical care, perioperative patients are at high risk of opioid-related adverse drug events. Existing methods of detection, such as trigger tools and manual chart review, are time-intensive which makes sustainability challenging. Using strategic rule design, computerized surveillance may be an efficient, pharmacist-driven model for event detection that leverages existing staff resources.

Methods

Computerized adverse drug event surveillance uses a logic-based rules engine to identify potential adverse drug events or evolving unsafe clinical conditions. We extended an inpatient rule (administration of naloxone) to detect opioid-related oversedation and respiratory depression to perioperative care at a large academic medical center. Our primary endpoint was the adverse drug event rate. For all patients with a naloxone alert, manual chart review was performed by a perioperative clinical pharmacist to assess patient harm. In patients with confirmed oversedation, other patient safety event databases were queried to determine if they could detect duplicate, prior, or subsequent opioid-related events.

Results

We identified 419 cases of perioperative naloxone administration. Of these, 101 were given postoperatively and 69 were confirmed as adverse drug events after chart review yielding a rate of 1.89 adverse drug events/1000 surgical encounters across both the inpatient and ambulatory settings. Our ability to detect inpatient opioid adverse drug events increased 22.7% by expanding surveillance into perioperative care. Analysis of historical surveillance data as well as a voluntary reporting database revealed that 11 of our perioperative patients had prior or subsequent harmful oversedation. Nine of these cases received intraoperative naloxone, and 2 had received naloxone in the post-anesthesia care unit. Pharmacist effort was approximately 3 hours per week to evaluate naloxone alerts and confirm adverse drug events.

Conclusion

A small investment of resources into a pharmacist-driven surveillance model gave great gains in organizational adverse drug event detection. The patients who experienced multiple events are particularly relevant to future studies seeking risk factors for opioid induced respiratory depression. Computerized surveillance is an efficient, impactful, and sustainable model for ongoing capture and analysis of these rare, but potentially serious events.
Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer
Authors: Pickard Mark R , Green Andrew R , Ellis Ian O , Caldas Carlos , Hedge Vanessa L , Mourtada-Maarabouni Mirna , Williams Gwyn T
Published: August 2009

Introduction

Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).

Methods

We have used RNA interference to downregulate Fau and Bcl-G expression, both simultaneously and independently, in breast cancer cells in vitro to determine the importance of their roles in apoptosis. Expression of Fau, Bcl-G and MELK was measured by quantitative RT-PCR in breast cancer tissue and in matched breast epithelial tissue from the same patients. Expression data of these genes obtained using microarrays from a separate group of patients were related to patient survival in Kaplan–Meier analyses.

Results

siRNA-mediated downregulation of either Fau or Bcl-G expression inhibited apoptosis, and the inhibition produced by combining the two siRNAs was consistent with control of Bcl-G by Fau. Fau expression is significantly reduced in breast cancer tissue and this reduction is associated with poor patient survival, as predicted for a candidate breast cancer tumour suppressor. In addition, MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene. Bcl-G expression is reduced in breast cancer tissue but decreased Bcl-G expression showed no correlation with survival, indicating that the most important factors controlling Bcl-G activity are post-translational modification (by Fau and MELK) rather than the rate of transcription of Bcl-G itself.

Conclusions

The combination of in vitro functional studies with the analysis of gene expression in clinical breast cancer samples indicates that three functionally interconnected genes, Fau, Bcl-G and MELK, are crucially important in breast cancer and identifies them as attractive targets for improvements in breast cancer risk prediction, prognosis and therapy.
Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study
Authors: Morelli Andrea , Ertmer Christian , Rehberg Sebastian , Lange Matthias , Orecchioni Alessandra , Cecchini Valeria , Bachetoni Alessandra , D'Alessandro Mariadomenica , Van Aken Hugo , Pietropaoli Paolo , Westphal Martin
Published: August 2009

Introduction

Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.

Methods

We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg-1·h-1), vasopressin (.03 U·min-1) or norepinephrine (15 μg·min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.

Results

There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 μg·min-1of norepinephrine, 1.3 μg·kg-1·h-1of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1at 48 hours; eachP< 0.05) and was associated with less rebound hypotension (P< 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1; eachP< 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P< 0.001 48 hours vs. BL).

Conclusions

The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.

Trial registration

ClinicalTrial.gov NCT00481572.
Transpulmonary thermodilution-derived cardiac function index identifies cardiac dysfunction in acute heart failure and septic patients: an observational study
Authors: Ritter Simon , Rudiger Alain , Maggiorini Marco
Published: August 2009

Introduction

There is limited clinical experience with the single-indicator transpulmonary thermodilution (pulse contour cardiac output, or PiCCO) technique in critically ill medical patients, particularly in those with acute heart failure (AHF). Therefore, we compared the cardiac function of patients with AHF or sepsis using the pulmonary artery catheter (PAC) and the PiCCO technology.

Methods

This retrospective observational study was conducted in the medical intensive care unit of a university hospital. Twelve patients with AHF and nine patients with severe sepsis or septic shock had four simultaneous hemodynamic measurements by PAC and PiCCO during a 24-hour observation period. Comparisons between groups were made with the use of the Mann-Whitney U test. Including all measurements, correlations between data pairs were established using linear regression analysis and are expressed as the square of Pearson's correlation coefficients (r2).

Results

Compared to septic patients, AHF patients had a significantly lower cardiac index, cardiac function index (CFI), global ejection fraction, mixed venous oxygen saturation (SmvO2) and pulmonary vascular permeability index, but higher pulmonary artery occlusion pressure. All patients with a CFI less than 4.5 per minute had an SmvO2 not greater than 70%. In both groups, the CFI correlated with the left ventricular stroke work index (sepsis: r2 = 0.30, P < 0.05; AHF: r2 = 0.23, P < 0.05) and cardiac power (sepsis: r2 = 0.39, P < 0.05; AHF: r2 = 0.45, P < 0.05).

Conclusions

In critically ill medical patients, assessment of cardiac function using transpulmonary thermodilution technique is an alternative to the PAC. A low CFI identifies cardiac dysfunction in both AHF and septic patients.
Iodine‐125 Radiotherapy for Choroidal Melanoma
Authors: Al Mahmoud Tahra , Mansour Magdi , Deschênes Jean , Edelstein Chaim , Burnier Miguel , Marcil Michel , Shenouda George , Corriveau Christine , Evans Michael
Published: August 2009

The objective was to evaluate the effect of the gender, size, and tumor location at the time of the diagnosis on the regression response of choroidal melanoma following plaque radiotherapy treatment. The paper is a longitudinal prospective study of 28 patients diagnosed with choroidal melanoma at McGill University Health Centre from 1997 to 2002. All patients were treated with episcleral iodine‐125 (I125) plaque radiotherapy. Plaques were inserted at the tumor site under echographic visualization. All patients had medium‐size tumors, except for three. Patients had periodic ophthalmic evaluation at 3 and 6 months post radiation treatment, followed by 6‐month intervals thereafter. Patients' mean age was 62 ± 15 years, 16 males and 12 females. Fifty percent of the tumors were located posterior to the equator with significant reduction in size at 12 months post plaque radiotherapy treatment. Significant regression was observed in all the tumor diameters at 5 years post treatment follow‐up. Reduction in the depth diameter was significant (P < 0.01) in both male and female groups post treatment. There was a 25% (P < 0.001) reduction in the medium size of tumors at 5‐year follow‐up. Tumors located posterior to the equator responded best to I125 plaque radiotherapy. Male patients responded better than females to treatment. Medium‐size melanoma responded well to plaque radiotherapy.
Update on Recent Developments for Patients with Newly Diagnosed Multiple Myeloma
Authors: Palumbo Antonio , Magarotto Valeria , Gay Francesca , Falco Patrizia , Bringhen Sara , Boccadoro Mario
Published: August 2009

Recent studies have demonstrated that novel therapeutic combinations are challenging melphalan and prednisone (MP) as the standard of care in elderly patients with multiple myeloma. Combination regimens containing bortezomib or thalidomide can achieve response rates, especially complete response rates, which are superior to those seen with standard MP alone, and offer new possibilities for this patient population.
Advances in the Management of Pediatric Central Nervous System Tumors
Authors: Abdullah Shaker , Qaddoumi Ibrahim , Bouffet Eric
Published: August 2009

Central nervous system tumors are the most common pediatric solid tumors and a leading cause of cancer‐related mortality and morbidity in this age group. Survival rates have improved significantly over the last decades for most of the tumor types, as a consequence of improvements in neuroimaging, neurosurgery and neuroanesthesia, radiation oncology, and medical oncology. The complexity of the management of these patients requires a multidisciplinary approach and has led to the emergence of a new subspecialty of pediatric neuro‐oncologists who are dedicated to the management and follow‐up of this population. This review highlights the most critical advances in the diagnostic and treatment modalities of pediatric brain tumors. A specific review of the most common tumor types discusses treatment options, controversies, and ongoing developments, with an emphasis on cooperative trials.
Attitudes, Perceptions, and Family Coping in Pediatric Cancer and Childhood Diabetes
Authors: Eapen Valsamma , Mabrouk AbdelAzim , Bin‐Othman Salem
Published: August 2009

The importance of psychosocial factors in psychological adjustment and coping in children with cancer and their families is well recognized. In this study, parental attitudes, children's self‐perceptions, and families' coping were studied in 38 children with leukemia, 30 children with juvenile diabetes, and 30 control subjects. Children with cancer scored themselves more negatively than their parents on all the subscales except scholastic competence, while children with diabetes scored negatively in the area of athletic competence. With regard to family coping, parental hope as well as social and family communication were the most important factors that contributed to better coping in children with leukemia, while parental education and health awareness were integral to better coping in children with diabetes. Awareness of family coping and understanding the domains of self‐competence and self‐worth, which are vulnerable in children with cancer, can help healthcare providers to target these issues and to offer appropriate psychosocial intervention.
Role of Tc99m MIBI SPECT in the Assessment of Treatment Response in Pharyngeal Carcinoma
Authors: Khawar Ambreen , Rafique Muhammad Asif , Jafri Rafaqat Ali , Saeed Shabana
Published: August 2009

The purpose of this study was to compare Tc99m MIBI SPECT imaging with computed tomography (CT) for assessment of post‐radiotherapy treatment response in pharyngeal carcinoma. Twenty‐two subjects took part in this study, which included six patients with nasopharyngeal carcinoma (Group I), three patients with oropharyngeal carcinoma and eight patients with hypopharyngeal carcinoma (Group II), and five control patients (Group III). All scans were analyzed qualitatively and quantitatively and correlated with findings on local examination and biopsy. Various indices such as ratios of nasopharynx, oropharynx, and hypopharynx to scalp (NSR, OSR, HSR), to nuchal muscles (NNR, ONR, HNR), and parotid glands (NPR, OPR, HPR) were calculated. The mean values of these above mentioned ratios calculated in the control group (Group III) were used as cutoff values to determine the presence or absence of tumor tissue in the patient groups (Groups I and II). The cutoff values calculated were 2.89 (NSR), 1.39 (NNR), 0.57(NPR), 3.83 (OSR), 1.81 (ONR), 0.83 (OPR), 2.86 (HSR), 1.73 (HNR), and 0.59 (HPR). The results revealed 100% sensitivity for primary nasopharyngeal tumors but less sensitivity for primary oropharyngeal and hypopharyngeal tumors (63.6%). Based on a relative decrease in tracer uptake, Tc99m MIBI SPECT scan was able to predict partial remission, complete remission, and no response on post‐therapy scans. There were three false‐negative results of disease progression in addition to evidence of disease eradication on CT scan. Thus Tc99m MIBI SPECT imaging has shown promising results in the detection of primary tumors and evaluation of treatment response much earlier than CT scan, which needs further exploration and large‐scale studies.
Surgical Management of Very Large Musculoskeletal Sarcomas
Authors: Abed Rafiq , Younge Derek
Published: August 2009

The management of almost all sarcomas in the musculoskeletal system includes surgery, although chemotherapy and radiotherapy also may play an important role in the treatment. The surgical treatment comprises complete resection of the tumor with a margin of normal tissue. This can be accomplished by local resection and then reconstruction of the resultant deficit, or amputation. Resection of the tumor without amputation, that is, limb‐salvage surgery, can be accomplished in 80% of cases and is generally preferred by the patient. The very large, neglected, or aggressive tumor, however, can make resection with a wide margin impossible or very difficult. Many large tumors will require amputation in order to be sure that the entire tumor is removed, as the priority is saving the patient's life, with limb preservation secondary. Even an amputation may be very difficult when the pelvic or shoulder girdle is involved. Sometimes the surgeon may agree to do a marginal resection when the patient or family absolutely refuses amputation, but they must be made to understand that this may compromise survival. In cases where there is circumferential skin involvement or projected loss, some unusual techniques, such as amputation‐replantation can be done, especially in the upper limb, where in spite of gross shortening, function can be much better than any prosthesis. Even if there are metastases present, sometimes amputation or even local resection is offered as palliation if the patient's life is made miserable by a large fungating tumor. Local resection of a huge tumor can be a formidable challenge to the surgeon, and the margin may consist of a few millimeters of compressed muscle. Good skin cover may be a major problem, and free tissue transfer may be necessary if local flaps are not possible. In all cases, one must ask if the resection‐reconstruction with all its complications and risk to the patient of recurrence is really better than an amputation.
The Use of a Vacuum‐assisted Biopsy Device (Mammotome) in the Early Detection of Breast Cancer in the United Arab Emirates
Authors: Faour Issam , Al‐Salam Suhail , El‐Terifi Hassan , El Taji Hakam
Published: August 2009

Stereotactic core needle biopsy has proven to be an accurate technique for evaluation of mammographically detected microcalcification. The development of the Mammotome biopsy system has led many medical centers to use this vacuum‐assisted device for the sampling of microcalcifications in mammographically detected nonpalpable breast lesions. Ninety‐six women underwent 101 stereotactic Mammotome core biopsies for mammographic calcifications over a 32‐month period in the Department of Surgery at Tawam Hospital, the national referral oncology center in the UAE. The stereotactic procedure was performed by surgeons using the Mammotome biopsy system. Microcalcifications were evident on specimen radiographs and microscopic sections in 96% and 87% of the cases, respectively. Excisional biopsy was recommended for diagnoses of atypical ductal hyperplasia or carcinoma. Patients with benign diagnoses underwent mammographic follow‐up. Eighty‐one lesions were benign, 5 atypical ductal hyperplasias and 14 carcinomas were diagnosed (2 invasive lobular carcinoma, 4 invasive ductal carcinoma, and 8 intraductal carcinomas in situ: 1 comedo, 1 cribriform, 6 mixed cribriform and micropapillary). Surgical excision in four patients with atypia on Mammotome biopsy (one was lost to follow‐up) showed atypical ductal hyperplasia. Surgical excision in seven patients diagnosed with intraductal carcinoma in situ (one patient lost to follow‐up) showed intraductal carcinoma with no evidence of microinvasion. Similar diagnoses were made in all the invasive ductal and lobular carcinomas in both Mammotome and excisional biopsies. A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was negligible for microcalcification diagnosed as intraductal carcinoma in situ on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling, diagnosis, and early detection of breast cancer.
An Immunohistochemistry Study of Tissue Bcl‐2 Expression and Its Serum Levels in Breast Cancer Patients
Authors: Alireza Andalib , Raheleh Shokohi , Abbass Rezaei , Mojgan Mokhtari , Mohamadreza Mohageri , Gholamreza Mohageri , Shadi Babazadeh
Published: August 2009

Variations in Bcl‐2 expression have been reported in malignant tissues with various origins. In the case of breast cancer, the involvement of Bcl‐2 overexpression in tumorigenicity and metastatic potential has been stated. However, association of tumor progression and loss of Bcl‐2 in tumor cells is also being investigated. Augmentation of plasma levels of Bcl‐2 was speculated in patients with metastatic breast cancer. The present study was designed to evaluate Bcl‐2 protein expression in breast tumor paraffin‐embedded fixed tissue and sought to investigate association with the Bcl‐2 protein release in patient serum, as well as its relationship with clinicopathological features. Immunohistochemistry methods were applied to breast tumor sections from 35 surgically removed patient samples and 35 normal or benign tissue samples. The sera taken from both the patient and control groups were tested for soluble Bcl‐2 (BMs244/3 Kit) using ELISA technique. Tumor type, grade, and size and patient menopause status and age were considered to analyze the association between these parameters. The analysis shows that 67.6% of the tumor sections were positive for Bcl‐2 expression and 32.4% negative. Bcl‐2 protein expression was positive in 57.1% of normal/benign section tumors. The Bcl‐2 serum levels were 3.6 ± 1.1 ng/mL in the patient group and 3.23 ± 0.06 ng/mL in the control group. A weak correlation was found between Bcl‐2 serum levels and tissue expression of the molecules (r= 0.382, P= 0.049). A negative association (but not statically significant) was obtained between Bcl‐2 and low‐grade stages (r=−0.375, P= 0.08). A positive and significant correlation was shown between Bcl‐2 and menopause (r= 0.523, P= 0.005) and between age and serum Bcl‐2 (r= 0.488, P= 0.011). Although a majority of the breast tumor tissue expresses Bcl‐2, the mean Bcl‐2 serum levels were not different between patient and control groups. The present data would lead us to use the Bcl‐2 expression in tissue at the level of protein expression or would suggest the use of mRNA levels, but the use of serum levels would be very limited for clinical purposes.
Validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for Arabic‐speaking Populations
Authors: Awad Manal A. , Denic Srdjan , El Taji Hakam
Published: August 2009

Information about quality of life in patients with cancer in Arab populations in 21 countries is inadequate. The objective of this study was to assess the psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer (EORTC) general quality of life questionnaire (QLQ‐C30) and of the breast cancer–specific questionnaire (QLQ‐BR23) in Arab breast cancer patients. The questionnaires were administered to 87 breast cancer patients 3 months after surgery. The mean age of patients was 48.6 years (SD: 9.9), 76% were married, all had staged disease (I, 9%; II, 46%; III, 44%; IV, 1%). The percentage of patients who underwent mastectomy and lumpectomy were 49% and 51%, respectively. Questionnaire reliability was assessed using Cronbach's alpha coefficient, in which the values were all >0.7, with the exception of cognitive function and pain in the QLQ‐C30 (Cronbach's alpha 0.67 and 0.51, respectively) and breast symptoms in the QLQ‐BR23 (Cronbach's alpha 0.50). The questionnaires' validity was confirmed using “known group comparisons,” which showed that the QLQ‐C30 discriminated between mastectomy and lumpectomy patients on the emotional and cognitive function scales (P < 0.001) and QLQ‐BR23 discriminated as well on the function scales and for systemic side effects (P < 0.001). For the most part, QLQ‐C30 and QLQ‐BR23 distinguished clearly between subgroups of patients differing in their Hospital Anxiety and Depression Scale. In summary, the Arabic versions of the EORTC QLQ‐C30 and QLQ‐BR23 are reliable and valid tools for assessment of quality of life in Arab patients with cancer.
Surgical Treatment of Pancreatic Cancer
Authors: Loos Martin , Kleeff Jörg , Friess Helmut , Büchler Markus W.
Published: August 2009

Pancreatic cancer is an aggressive disease with an overall 5‐year survival rate of less than 5%. Up to date, surgical resection represents the basis of treatment for localized pancreatic cancer and remains the only chance for cure. Due to continuous improvements in surgical techniques and perioperative care, pancreatic resections have evolved into safe surgical procedures with low mortality and acceptable morbidity rates for experienced surgeons in high‐volume centers. Recently, more aggressive approaches including extended lymphadenectomy, vascular resection, surgery for metastastic or recurrent disease, and multimodal regimens have been suggested to improve long‐term outcome. This article provides an overview on current standard procedures and summarizes new strategies in the surgical treatment of pancreatic cancer.
Profile of Patients with Colorectal Cancer at a Tertiary Care Cancer Hospital in Pakistan
Authors: Anwar Natasha , Badar Farhana , Yusuf Muhammad Aasim
Published: August 2009

The following study describes the basic demography of colorectal cancer patients and characteristics of the disease seen at a regional tertiary care cancer hospital. The study highlights the influence of gender and age on the occurrence of this malignancy in patients in Pakistan. In general, this population shares many epidemiological features of developing countries for colorectal carcinoma. These include a younger age at presentation (mean age of patients was 46.5 years), subsite distribution (72.5% had left‐sided tumors), and delayed presentation of the disease in an advanced stage. We stress the significance of public awareness regarding colorectal cancer to improve the outcome.
The Transforming Functions of PI3‐kinase‐γ Are Linked to Disruption of Intercellular Adhesion and Promotion of Cancer Cell Invasion
Authors: Attoub Samir , De Wever Olivier , Bruyneel Eric , Mareel Marc , Gespach Christian
Published: August 2009

The involvement of phosphoinositide 3‐kinases class IA (PI3K‐α and ‐β) in cancer cell proliferation, survival, motility, and invasiveness is now well established. However, the possible contribution of the class IB PI3Kγ in cancer cell transformation remains to be explored. In this study, we have stably transfected the PI3Kγ‐deficient human colon cancer cell line HCT8/S11 with expression vectors encoding either wild‐type PI3Kγ, its plasma membrane targeted form CAAX‐PI3Kγ, or the PI3Kγ lipid and protein kinase‐dead mutant (CAAX‐K832R). We provide evidence that the constitutively active CAAX‐PI3Kγ variant induced collagen type I invasion in HCT8/S11 cells through disruption of cell–cell adhesion, with no apparent impact on cell proliferation and motility. The proinvasive activity of CAAX‐PI3K‐γ was abolished by pharmacological inhibitors targeting PI3‐K activities (wortmannin), Rho‐GTPases, and the Rho‐Rho kinase axis (C3T exoenzyme and Y27632, respectively). Conversely, the wild‐type PI3Kγ and its double mutant CAAX‐K832R were ineffective on cancer cell invasion measured under control or stimulated conditions operated with the proinvasive agents leptin and intestinal trefoil factor. Taken together, our data indicate that PI3Kγ exerts transforming functions via several mechanisms in human colon epithelial cancer cells, including alterations of homotypic cell–cell adhesion and induction of collagen type I invasion through canonical proinvasive pathways.
New Developments in the Surgical Therapy of Cervical Carcinoma
Authors: Dornhöfer Nadja , Höckel Michael
Published: August 2009

For almost a century abdominal radical hysterectomy has been the standard surgical treatment of early‐stage macroscopic carcinoma of the uterine cervix. The excessive parametrial resection of the original procedures of Wertheim, Okabayashi, and Meigs has later been “tailored” to tumor extent. Systematic pelvic and eventually periaortic lymph node dissection is performed to identify and treat regional disease. Adjuvant (chemo)radiation therapy is liberally added to improve locoregional tumor control when histopathological risk factors are present. The therapeutic index of the current surgical treatment, particularly if combined with radiation, appears to be inferior to that of primary chemoradiation as an oncologically equivalent therapeutic alternative. Several avenues of new conceptual and technical developments have been used since the 1990s with the goal of improving the therapeutic index. These are: surgical staging, including sentinel node biopsy and nodal debulking; minimal access and recently robotic radical hysterectomy; fertility‐preserving surgery; nerve‐sparing radical hysterectomy; total mesometrial resection based on developmentally defined surgical anatomy; and supraradical hysterectomy. The superiority of these new developments over the standard treatment remains to be demonstrated by controlled prospective trials. Multimodality therapy including surgery for locally advanced disease represents another area of clinical research. Both neoadjuvant chemotherapy followed by radical surgery, with or without adjuvant radiation, and completion surgery after (chemo)radiation are feasible and have to be compared to primary chemoradiation as the new nonsurgical treatment standard. Surgical treatment of postirradiation persisting or recurrent cervical carcinoma has been traditionally limited to pelvic exenteration for central disease. Applying the principle of developmentally derived anatomical compartments increases R0 resectability. The laterally extended endopelvic resection allows even the extirpation of a subset of visceral pelvic side wall tumors with clear margins. Many questions regarding the indication for these “ultraradical” operations, the surgery of irradiated tissues, and the optimal reconstructive procedures are still open and demand multi‐institutional controlled trials to be answered.
Cancer Pain and Analgesia
Authors: Christo Paul J. , Mazloomdoost Danesh
Published: August 2009

Pain ranges in prevalence from 14–100% among cancer patients and occurs in 50–70% of those in active treatment. Cancer pain may result from direct invasion of tumor into nerves, bones, soft tissue, ligaments, and fascia, and may induce visceral pain through distension and obstruction. Cancer pain is multifaceted. Clinicians may describe cancer pain as acute, chronic, nociceptive (somatic), visceral, or neuropathic. Despite implementation of the WHO guidelines, reports of undertreatment of cancer pain persist in various clinical settings and in spite of decades of work to reduce unnecessary discomfort. Substantial obstacles to adequate pain relief with opioids include specific concerns of patients themselves, their family members, physicians, nurses, and the healthcare system. The WHO analgesic ladder serves as the mainstay of treatment for the relief of cancer pain in concert with tumoricidal, surgical, interventional, radiotherapeutic, psychological, and rehabilitative modalities. This multidimensional approach offers the greatest potential for maximizing analgesia and minimizing adverse effects. Primary therapies are directed at the source of the cancer pain and may enhance a patient's function, longevity, and comfort. Adjuvant therapies include nonopioids that confer analgesic effects in certain medical conditions but primarily treat conditions that do not involve pain. Nonopioid medications (over‐the‐counter agents) are useful in the management of mild to moderate pain, and their continuation through step 3 of the WHO ladder is an option after weighing a drug's risks and benefits in individual patients. Symptomatic treatment of severe cancer pain should begin with an opioid, regardless of the mechanism of the pain. They are very effective analgesics, titrate easily, and offer a favorable risk/benefit ratio. Cancer pain remains inadequately controlled despite the diagnostic and therapeutic means of ensuring that patients feel comfortable during their illness. Therefore, all practitioners need to make control of cancer pain a professional duty, even if they can only use the most basic and least expensive analgesic medications, such as morphine, codeine, and acetaminophen, to reduce human suffering.
In Vitro Effects of Tea Polyphenols on Redox Metabolism, Oxidative Stress, and Apoptosis in PC12 Cells
Authors: Raza Haider , John Annie
Published: August 2009

Tea polyphenols, especially catechins, have been reported to be potent antioxidants and beneficial in oxidative stress–related diseases including cancer. Numerous animal and cell culture models demonstrate anticancer effects of tea catechins. Experimental and epidemiological evidence suggests the use of black tea polyphenols (BTP), green tea catechins (especially epigallocatechin gallate [EGCG]), and other polyphenols in preventing the progression of cancer both in animal and human populations. In the present study, we have demonstrated alterations in oxidative stress and redox metabolism using an isolated cell‐free system and also in PC12 cancer cells after treatment with EGCG and BTP. We have demonstrated that tea catechins, alter the production of reactive oxygen species, glutathione metabolism, lipid peroxidation, and protein oxidation under in vitro conditions. We have also demonstrated that EGCG and BTP affect redox metabolism under cell culture conditions. Induction of apoptosis was observed, after the treatment with tea polyphenols, as shown by increased DNA breakdown and activation of the apoptotic markers, cytochrome c, caspase 3, and poly‐(ADP‐ribose) polymerase. These results may have implications in determining the chemopreventive and therapeutic use of tea catechins in vivo.
The Swi2/Snf2 Bromodomain Is Important for the Full Binding and Remodeling Activity of the SWI/SNF Complex on H3‐ and H4‐acetylated Nucleosomes
Authors: Awad Salma , Hassan Ahmed H.
Published: August 2009

The SWI/SNF chromatin‐remodeling complex contains a bromodomain in its Swi2/Snf2 subunit that helps tether it to acetylated promoter nucleosomes. To study the importance of this bromodomain in the SWI/SNF complex, we have compared the nucleosome‐binding and the chromatin‐remodeling activities of the SWI/SNF to a mutant complex that lacks the Swi2/Snf2 bromodomain. Here we show that the SWI/SNF complex deleted of the Swi2/Snf2 bromodomain cannot bind to SAGA‐ or NuA4‐acetylated nucleosomes as well as the wild‐type complex. Moreover, we show that this reduced binding leads to partial remodeling of these acetylated nucleosome templates by the Δbromodomain SWI/SNF complex. These results demonstrate that the Swi2/Snf2 bromodomain is required for the full binding and functional activity of the SWI/SNF complex on H3‐ and H4‐acetylated nucleosomes.
Akt Depletion Is an Important Determinant of L929 Cell Death following Heat Stress
Authors: Galadari Sehamuddin , Thayyullathil Faisal , Hago Abdulkader , Patel Mahendra , Chathoth Shahanas
Published: August 2009

Exposure of mammalian cells to heat stress causes impairment of numerous physiological functions and activates a number of signaling pathways. Some of these pathways, such as induction of heat‐shock proteins and activation of Akt, enhance the ability of cells to survive heat stress. On the other hand, heat stress can trigger cell‐death signaling via activation of the stress‐activated protein kinase/c‐Jun NH2‐terminal kinase (SAPK/Jnk). Recently, it has been shown that kinases activated by heat stress can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate the activity of the cell death and survival pathways. We have found that Akt plays a central role in determining the fate of L929 fibroblast cells exposed to heat stress. In our experiments heat stress causes Akt depletion and L929 cells to undergo cell death. Heat‐shock protein 70 (Hsp70) is known to prevent stress‐induced cell death by interfering with the SAPK/Jnk signaling pathway. In our study, there is a very high level of induction of Hsp70, yet this is not sufficient to rescue Akt depletion and L929 from cell death. The Akt depletion is specific, since actin protein level does not change during the heat stress. Moreover, our studies show that L929 cells can recover from a short‐term heat shock, whereby, Akt level is returned to normal following recovery from heat shock. Therefore, it appears that the fate of the prolonged heat‐stressed fibroblast cells is determined by Akt level, and that return of Akt protein level to normal prevents cell death.
Neural Correlates of Nouns and Verbs in Early Bilinguals
Authors: Chan Alice H.D. , Luke Kang‐Kwong , Li Ping , Yip Virginia , Li Geng , Weekes Brendan , Tan Li Hai
Published: August 2009

Previous neuroimaging research indicates that English verbs and nouns are represented in frontal and posterior brain regions, respectively. For Chinese monolinguals, however, nouns and verbs are found to be associated with a wide range of overlapping areas without significant differences in neural signatures. This different pattern of findings led us to ask the question of where nouns and verbs of two different languages are represented in various areas in the brain in Chinese–English bilinguals. In this study, we utilized functional magnetic resonance imaging (fMRI) and a lexical decision paradigm involving Chinese and English verbs and nouns to address this question. We found that while Chinese nouns and verbs involved activation of common brain areas, the processing of English verbs engaged many more regions than did the processing of English nouns. Specifically, compared to English nouns, English verb presentation was associated with stronger activation of the left putamen and cerebellum, which are responsible for motor function, suggesting the involvement of the motor system in the processing of English verbs. Our findings are consistent with the theory that neural circuits for linguistic dimensions are weighted and modulated by the characteristics of a language.
Two Forms of Implicit Learning in Young Adults with Dyslexia
Authors: Bennett Ilana J. , Romano Jennifer C. , Howard, Jr James H. , Howard Darlene V.
Published: August 2009

Implicit learning is thought to underlie the acquisition of many skills including reading. Previous research has shown that some forms of implicit learning are reduced in individuals with dyslexia (e.g., sequence learning), whereas other forms are spared (e.g., spatial context learning). However, it has been proposed that dyslexia‐related motor dysfunction may have contributed to the implicit sequence learning deficits reported earlier. To assess implicit sequence learning in the absence of a motor sequence, 16 young adults diagnosed with dyslexia (20.6 ± 1.5 years) and 18 healthy controls (20.8 ± 2.0 years) completed a triplet frequency learning task (TRIP) that involved learning a sequential regularity in which the location of certain events followed a repeating pattern, but motor responses did not. Participants also completed the spatial contextual cueing task (SCCT), which involved learning a spatial regularity in which the location of distractors in some visual arrays predicted the target location. In addition, neuropsychological tests of real‐word and pseudo‐word reading were administered. TRIP task analyses revealed no between‐group differences in pattern learning, but a positive correlation between individual learning scores and reading ability indicated that poor readers learned less well than did good readers. Thus, earlier reports of reduced implicit sequence learning in dyslexics cannot be entirely accounted for by motor sequencing deficits. No significant correlations or group differences in learning were found for SCCT. These findings offer additional evidence for a link between poor reading and impaired implicit sequence learning.