Urinary BLACAT1 as a non-invasive biomarker for bladder cancer.

BACKGROUND: Bladder cancer (BC) is recorded as the fifth most common cancer worldwide with high morbidity and mortality. The most urgent problem in BCs is the high recurrence rate as two-thirds of non-muscle-invasive bladder cancer (NMIBC) will develop into muscle-invasive bladder cancer (MIBC), which retains a feature of rapid progress and metastasis. In addition, only a limited number of biomarkers are available for diagnosing BC compared to other cancers. Hence, finding sensitive and specific biomarkers for predicting the diagnosis and prognosis of patients with BC is critically needed. Therefore, this study aimed to determine the expression and clinical significance of urinary lncRNA BLACAT1 as a non-invasively diagnostic and prognostic biomarker to detect and differentiate BCs stages. METHODS AND RESULTS: The expression levels of urinary BLACAT1 were detected by qRT-PCR assay in seventy (70) BC patients with different TNM grades (T0-T3) and twelve (12) healthy subjects as control. BLACAT1 was downregulated in superficial stages (T0 = 0.09 ± 0.02 and T1 = 0.5 ± 0.1) compared to healthy control. Furthermore, in the invasive stages, its levels started to elevate in the T2 stage (1.2 ± 0. 2), and higher levels were detected in the T3 stage with a mean value of (5.2 ± 0.6). This elevation was positively correlated with disease progression. Therefore, BLACAT1 can differentiate between metastatic and non-metastatic stages of BCs. Furthermore, its predictive values are not like to be influenced by schistosomal infection. CONCLUSIONS: Upregulation of BLACAT1 in invasive stages predicted an unfavorable prognosis for patients with BCs, as it contributes to the migration and metastasis of BCs. Therefore, we can conclude that urinary BLACAT1 may be considered a non-invasive promising metastatic biomarker for BCs.

Prognostic Values of MicroRNA-21 and Ki-67 in Diffuse Large B-Cell Lymphoma Patients: Egyptian Experience.

BACKGROUND: MicroRNA-21 (miR-21) is a small non-coding RNA which influences tumorigenesis by inhibiting the expression of target genes. Ki-67 is a nucleolar antigen highly correlated with the rate of proliferating cells. In this study, we aimed to evaluate the prognostic impact of miR-21 and Ki-67 in DLBCL disease in a cohort of Egyptian patients. METHODS: We prospectively enrolled 53 newly diagnosed DLBCL patients. RT-PCR was used to evaluate the plasma expression levels of miR-21. Tissue Ki-67 was assessed using immunohistochemistry (IHC) of lymph node biopsy sections. Overall survival (OS) and progression free survival (PFS) were the primary outcomes. RESULTS: miR-21 expression was significantly higher in patients with DLBCL in comparison to controls (p < 0.001). The median Ki-67 expression was 70% and positivity ranged from 25% to 100%. Response to treatment was achieved in 23 patients (43.4%). Higher miR-21 was associated with poor response to treatment (p = 0.03). Although patients' age was a significant predictor of OS in univariate analysis, none of the studied factors could predict OS in multivariate analysis. However, we found that Ki-67 expression was a significant predictor of PFS in both univariate and multivariate analyses. CONCLUSIONS: The study suggested that plasma miR-21 might be a valuable non-invasive prognostic marker of response to treatment in DLBCL patients. Moreover, Ki-67 is a potential significant predictor of both OS and PFS in those patients.

Medical Oncology Education in Egypt Over the Past 50 Years: the Experience of the National Cancer Institute of Cairo University.

This manuscript outlines the progress of education in the field of medical oncology in Egypt over the past 50 years. The manuscript illustrates the origin of the Egyptian medical oncology program since the creation of the only specialized cancer center in the country, the National Cancer Institute of Cairo University (NCI-Cairo) in 1969, from Cairo University Medical School. The manuscript also outlines the NCI-Cairo's educational program for developing a cadre of academic medical oncologists for NCI-Cairo, other Egyptian medical institutions, and countries in the Middle East and Africa. We also emphasize the capacity building that resulted over the past 50 years from academic and professional standpoints, the changing curriculum in medical oncology, and the differences between the medical oncology and clinical oncology education programs in the country. Medical oncology research resulted from international collaborations and highlighted needs for cancer prevention and control. Finally, we propose possible future directions for medical oncology education and research in the country and a roadmap for low- and middle-income countries (LMICs) that are developing their medical oncology programs.

Impact of serum levels of IL-18 and soluble IL-2 receptor on the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP regimen.

AIM & METHODS: To assess the impact of pretreatment serum levels of IL-18 and soluble IL-2 receptor (sIL-2R) on the clinical outcome of patients with diffuse large B-cell lymphoma treated with an R-CHOP protocol. Total 73 patients were included. RESULTS: Elevated serum IL-18 (using mean as cutoff) was associated with numerically lower complete remission, and 3-year disease-free survival rates; however, the difference was not statistically significant. Nevertheless, the 3-year overall survival rates were significantly more favorable for the lower serum level group. Correspondingly, the complete remission, 3-year disease-free survival and overall survival rates for patients with low pretreatment sIL-2R levels were significantly better than individuals with higher levels. CONCLUSION: There is a growing body of evidence supporting the utility of pretreatment serum levels of sIL-2R and IL-18 as prognostic factors in diffuse large B-cell lymphoma patients.

The prognostic impact of hypermethylation for a panel of tumor suppressor genes and cell of origin subtype on diffuse large B-cell lymphoma.

Diffuse Large B-cell lymphoma (DLBCL) is an aggressive disease with heterogeneous outcome and marked variable response to chemotherapy. We assessed promoter hypermethylation (PM) for a panel of tumor suppressor genes in 75 DLBCLs compared to 20 lymphoid hyperplasia (LH) and 30 normal control, using methylation specific PCR. Results were correlated to patients' clinic-pathological characteristics, immunophenotyping, and patients' outcome. DAPK1, RUNX3, MT1G, MGMT, CDH1 and p16 PM were detected in 38.7% (29/75), 49.3% (37/75), 46.7% (35/75), 44% (33/75), 49.3% (37/75) and 42.7% (32/75);respectively, of DLBCL patients compared to LH group (P < 0.05). Aberrant PM of RUNX3, MGMT, CDH1 and p16 was significantly higher in non-germinal central B-cell like (non-GCB) compared to GCB (58.3% vs. 33.3%, 56.2% vs. 22.2, 62.5% vs. 25.9, and 56.2% vs. 18.5%, respectively). PM of studies genes in DLBCL associated significantly with worse survival outcome and resistance to chemotherapy (P ≤ 0.01). In non-GCB group, DAPK1, MT1G, RUNX3, CDH1 and p16 PM associated significantly with reduced DFS (P ≤ 0.004) and OS (P ≤ 0.015). Multivariate analysis indicated that RUNX3 and CDH1 PM were independent prognostic factors for OS (P = 0.03 and 0.04; respectively), while DAPK1, RUNX3 and MT1G PM were independent prognostic factors for DFS (P = 0.002, 0.037& 0.007; respectively). DAPK1, RUNX3, MT1G, CDH1 and p16 PM are promising prognostic and/or predictive markers for non-GCB independent of IPI. Upregulation of those genes using new demethylating agents is a promising approach that sensitize chemoresistant DLBCL patients, especially the non-GCB subtype.

Microsatellite instability profiling in Egyptian bladder cancer patients: A pilot study.

Microsatellite alterations have been implicated in the pathogenesis of many cancers; however, they are still not well addressed in the bladder cancer (BC) of Egyptian population. We assessed microsatellite instability (MSI) profile and loss of heterozygosity (LOH) using 13 microsatellite markers in tumor tissue samples and urine sediments obtained from 30 Egyptian patients with BC. The concordance between MSI in tumor tissue and urine samples was determined, and correlated to relevant clinicopathologic features. We found that MSI was more frequent than LOH (100% and 46.7%, respectively). D16S310, MBP, and IFN-α showed the highest MSI frequency in urine samples (70%, 70%, and 66.67%, respectively), while MBP, ACTBP2, and D9S171 (66.67%, 63.33%, and 60%, respectively) were the most frequently detected in tumor tissues. All assessed MSI markers correlated significantly with pathologic subtype (being more frequent in TCC) and with hematuria. The concordance between tissue and urine samples was statistically significant for D16S476, D9S171, FGA, and ACTBP2 (P = 0.04, 0.015, 0.02, and 0.007, respectively). When we combined D16S476 and D9S171, the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of BC were 80.0%, 75.0%, 82.8%, and 71.4%, respectively. Accordingly, we concluded that MSI in urine sediments could be a potential tool for the diagnosis of BC.

Adjuvant Sandwich Chemotherapy Plus Radiotherapy vs Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer After Radical Cystectomy: A Randomized Phase 2 Trial.

Importance: Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era. Objective: To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone. Design, Setting, and Participants: A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease. Interventions: Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin. Main Outcome and Measure: Locoregional recurrence-free survival. Results: The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm. Conclusions and Relevance: Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials. Trial Registration: clinicaltrials.gov Identifier: NCT01734798.

Differential expression of viral agents in lymphoma tissues of patients with ABC diffuse large B-cell lymphoma from high and low endemic infectious disease regions.

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed lymphomas worldwide. Environmental factors, such as viruses and bacteria, may contribute to cancer development through chronic inflammation and the integration of oncogenes, and have previously been indicated in cervical cancer, hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In the present study, the presence of microbial agents was analyzed in the lymphoma tissue of patients with activated B-cell like (ABC) DLBCL. The present study compared two groups of patients from geographically varied regions that possess a difference in the prevalence of viral and other microbial agents. The patient populations were from Sweden (a low endemic infectious disease region) and Egypt (a high endemic infectious disease region). A differential expression of several viruses in lymphoma tissues was noted when comparing Swedish and Egyptian patients. JC polyomavirus (JCV) was detected in Swedish and Egyptian patients and, uniquely, the complete hepatitis B virus (HBV) genome was detected only in Egyptian lymphoma patients. None of these viruses were detected in control lymph tissues from Sweden or Egypt. In total, 38% of the Egyptian patients were found to have HBV surface antigens (HBsAgs) in their serum; however, HBsAgs were not found in any of the Swedish patients. The percentage of serum HBsAgs in Egyptian patients with ABC DLBCL was significantly increased compared with the general Egyptian population (P<0.05). The present study may support a notion that viral agents, including JCV and HBV, may be involved in the tumorigenesis of DLBCL in regions of high infectious disease.

Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats.

Plasmonic photothermal therapy (PPTT) was introduced as a promising treatment of cancer. This work was conducted to evaluate the cytotoxic effect of intratumoral (IT) injection of 75µg gold nanorods (GNRs)/kg of body weight followed by direct exposure to 2 w/cm2 near infra-red laser light for 10min on ablation of mammary tumor in 10 dogs and 6 cats. Complete blood count (CBC), liver and kidney function were checked before the start of treatment and one month after injection of GNRs. Results showed that 62.5% (10/16), 25% (4/16) and 12.5% (2/16) of treated animals showed complete remission, partial remission and no response, respectively. Tumor was relapsed in 4 cases of initially responding animals (25%). Overall survival rate was extended to 315.5±20.5days. GNRs have no toxic effect on blood profile, liver or kidney functions. In conclusion, GNRs can be safely used for treatment of mammary tumors in dogs and cats.

Differentially expressed genes in metastatic advanced Egyptian bladder cancer.

BACKGROUND: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. MATERIALS AND METHODS: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. RESULTS: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. CONCLUSIONS: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

Cancer incidence in egypt: results of the national population-based cancer registry program.

Background. This paper aims to present cancer incidence rates at national and regional level of Egypt, based upon results of National Cancer Registry Program (NCRP). Methods. NCRP stratified Egypt into 3 geographical strata: lower, middle, and upper. One governorate represented each region. Abstractors collected data from medical records of cancer centers, national tertiary care institutions, Health Insurance Organization, Government-Subsidized Treatment Program, and death records. Data entry was online. Incidence rates were calculated at a regional and a national level. Future projection up to 2050 was also calculated. Results. Age-standardized incidence rates per 100,000 were 166.6 (both sexes), 175.9 (males), and 157.0 (females). Commonest sites were liver (23.8%), breast (15.4%), and bladder (6.9%) (both sexes): liver (33.6%) and bladder (10.7%) among men, and breast (32.0%) and liver (13.5%) among women. By 2050, a 3-fold increase in incident cancer relative to 2013 was estimated. Conclusion. These data are the only available cancer rates at national and regional levels of Egypt. The pattern of cancer indicated the increased burden of liver cancer. Breast cancer occupied the second rank. Study of rates of individual sites of cancer might help in giving clues for preventive programs.

Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation.

BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer have a significant risk of distant metastases. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin (GC) in improving the outcome of this group of patients over radical cystectomy alone. PATIENTS AND METHODS: A total of 114 patients with newly diagnosed bladder cancer (T3-4, N0-2, M0) were randomized to radical cystectomy alone or initial 3 cycles of GC, then managed according to response. Patients who achieved complete response completed 6 cycles of GC followed by local radiation therapy (RT) only. If tumors were downstaged to T1, complete transurethral resection was done, followed by 3 cycles of GC and then RT. Patients with partial response underwent radical cystectomy followed by 3 cycles of GC. Patients with stable disease or disease progression underwent radical cystectomy. RESULTS: The overall response rate to GC was 55.1%, and complete response was achieved in 28.6%. The 3-year overall survival (OS) was 51.9% versus 51.2% in the chemotherapy and surgery arms, respectively (P = .399). The 3-year disease-free survival was 31.8% in the chemotherapy arm and 45.1% in the surgery arm (P = .06). Bladder preservation was achieved in 22.5% of patients in the neoadjuvant arm. OS was 78% in responding patients and 100% in patients with complete response. CONCLUSION: Neoadjuvant GC did not improve survival in locally advanced bladder cancer over radical cystectomy alone. However, bladder preservation was feasible, and OS in responding patients was impressive. Therefore, predictive models to select patients are needed. This is the largest prospective study of squamous cell carcinoma and transitional cell carcinoma using neoadjuvant GC.

Developing cancer control plans in Africa: examples from five countries.

The creation and implementation of national cancer control plans is becoming increasingly necessary for countries in Africa, with the number of new cancer cases per year in the continent expected to reach up to 1·5 million by 2020. Examples from South Africa, Egypt, Nigeria, Ghana, and Rwanda describe the state of national cancer control plans and their implementation. Whereas in Rwanda the emphasis is on development of basic facilities needed for cancer care, in those countries with more developed economies, such as South Africa and Nigeria, the political will to fund national cancer control plans is limited, even though the plans exist and are otherwise well conceived. Improved awareness of the increasing burden of cancer and increased advocacy are needed to put pressure on governments to develop, fund, and implement national cancer control plans across the continent.

Patients with activated B-cell like diffuse large B-cell lymphoma in high and low infectious disease areas have different inflammatory gene signatures.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with an association with inflammation and viral infections. We hypothesize that environmental factors may be involved in the pathogenesis of DLBCL. In this study, we compared gene expression profiles of lymph node tissues from patients with DLBCL from two different geographical areas with diverse environmental exposures. Specimens from Egyptian and Swedish patients with DLBCL as well as controls were studied. Gene expression analysis using microarray and quantitative polymerase chain reaction demonstrated significantly higher expression of signal transducer and activator of transcription 3 (STAT3) in Swedish as compared to Egyptian patients and control materials from both countries. This was confirmed at protein level using confocal microscopy. The receptor tyrosine kinase ROR1, a "survival factor" for malignant cells, was overexpressed and significantly related to the STAT3 expression pattern. The difference in the expression of genes involved in inflammatory responses and in the tumorigenic process of DLBCL might relate to infectious agents and/or other environmental exposures.

Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients.

BACKGROUND/OBJECTIVE: Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones. METHODS: This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO), fructosamine, lactate dehydrogense (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE) and tumor necrosis factor alpha (TNF-α). In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients. CONCLUSIONS: It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer.

Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the Breast Health Global Initiative consensus, 2010.

The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health-care systems.

Breast cancer management in middle-resource countries (MRCs): consensus statement from the Breast Health Global Initiative.

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.

Cathepsin B: a potential prognostic marker for inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC. METHODS: In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups. RESULTS: Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC. CONCLUSIONS: CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.

Gem-(R)CHOP versus (R)CHOP: a randomized phase II study of gemcitabine combined with (R)CHOP in untreated aggressive non-Hodgkin's lymphoma--EORTC lymphoma group protocol 20021 (EudraCT number 2004-004635-54).

BACKGROUND: Despite recent improvements, many patients with aggressive non-Hodgkin's lymphoma (NHL) ultimately succumb to their disease. Therefore, improvements in front-line chemotherapy of aggressive NHL are needed. Gemcitabine is active in lymphoma. METHODS: We performed a randomized phase II trial of the addition of gemcitabine to standard CHOP chemotherapy with or without rituximab [(R)CHOP]. The trial was also designed to determine the maximal tolerated dose (MTD) of gemcitabine in this combination. Patients with previously untreated aggressive NHL were randomized to receive either eight cycles of (R)CHOP given every 3 wk or (R)CHOP combined with gemcitabine [Gem-(R)CHOP]. RESULTS: Twenty-five patients were enrolled in the trial before early closure. Twelve were randomized to Gem-(R)CHOP and 13 to (R)CHOP. MTD of gemcitabine was 800 mg/m(2) given on days 1 and 8; dose-limiting toxicity was hematologic. Five patients (42%) treated with Gem-(R)CHOP achieved complete response in comparison with 10 (77%) treated with (R)CHOP. Median time to treatment failure was 1.5 yr for Gem-(R)CHOP and 3.1 yr for (R)CHOP. Three patients receiving Gem-(R)CHOP had serious pulmonary toxicity, when compared to none receiving (R)CHOP. One patient died of pneumonitis. CONCLUSIONS: In this group of patients, addition of gemcitabine did not seem to improve outcomes. Gem-(R)CHOP in previously untreated patients with aggressive NHL occasionally results in severe, potentially fatal, pulmonary toxicity.