Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.     

Residing in a food desert is associated with an increased risk of readmission following esophagectomy for cancer

BackgroundNutritional status is related to treatment outcomes for esophageal cancer. Residing in a food desert (FD) has been associated with worse outcomes in breast and colon cancer. We assessed the association of residing in a FD on 30-day outcomes of esophageal cancer patients who received tri-modality therapy.MethodsA retrospective review of patients who underwent esophagectomy (1/2015 to 7/2020, in New Hampshire, USA) was performed. Patients were excluded if they did not undergo neo-adjuvant treatment, required treatment outside of standard Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) protocol, or lacked both pre and post neo-adjuvant treatment computed tomography (CT) scans for review. Demographics, nutrition parameters, treatment characteristics, 30-day complications and 90-day mortality were reviewed. FD status was defined by the United States Department of Agriculture (USDA) Food Access Research Atlas and cross-referenced with patients’ home zip code. Readmission was defined as readmission to any hospital for any reason within 30-day of discharge. Univariable analysis was conducted using Student’s t-test or Wilcoxon rank-sum for continuous variables, and Fisher’s exact test for categorical variables. Multivariable logistic regression was then used to model readmission status on FD status adjusted for measures statistically associated with readmission status at the P<0.10 in univariable analyses.ResultsSeventy-eight patients were included in the analysis. Overall pre-treatment prevalence of sarcopenia was 11.5% (9/78) and did not vary by FD status. Univariable analysis, demonstrated few significant differences between those who were readmitted and those who were not. On unadjusted analysis, patients who lived in a FD were 5 times more likely to be readmitted [5.16; 95% confidence interval (CI): 1.70–15.67] compared to those who did not. Residing in a FD remained a significant risk factor for readmission after adjustment for operative time, discharge to a rehabilitation facility and development of a grade III/IV complication [adjusted odds ratio (OR): 6.38; 95% CI: 1.45–28.08].ConclusionsOur data suggest that residing in a FD is a prognostic factor for readmission after tri-modality therapy for esophageal cancer. Clinicians need to be aware that previously established nutritional markers may not completely capture nutritional status and living in a FD may significantly increase the risk of readmission in these patients.     

3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。     

The prognostic value of vascular endothelial growth factors (VEGFs)-A and -B and their receptor, VEGFR-1, in invasive breast carcinoma

OBJECTIVES: Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive breast carcinoma remains unclear. METHODS: We immunohistochemically examined the expression pattern of VEGF-A, VEGF-B and VEGFR-1 in 177 invasive breast carcinomas in relation to clinicopathological parameters, p53, c-erbB2 proteins expression and patients' survival. RESULTS: VEGF-A, VEGF-B and VEGFR-1 were immunodetected predominantly in the cytoplasm of the malignant cells. None of the studied markers correlated with any of the clinicopathological parameters, other than stromal VEGFR-1 which inversely correlated with PR (p=0.021). Cancerous VEGF-A and stromal VEGFR-1 were positively related to p53 (p=0.016 and p=0.033, respectively). Cancerous VEGF-B was positively associated with c-erbB-2 (p=0.045) and was found to exert an unfavorable impact on both disease-free and the overall survival of the node-positive patients (p=0.05 and p=0.029, respectively). Cancerous VEGFR-1 was recognized as being an independent poor prognostic indicator (p=0.037). CONCLUSION: These findings suggest that, while VEGF-B seems to be useful as a prognostic indicator only in node-positive patients, VEGFR-1 may be an independent poor prognosticator in patients with invasive breast carcinoma.     

Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

Patient contracts for chronic medical conditions: Scoping review

ObjectiveTo describe how and why patient contracts are used for the management of chronic medical conditions.Data sourcesA scoping review was conducted in the following databases: MEDLINE, Embase, AMED, PsycInfo, Cochrane Library, CINAHL, and Nursing & Allied Health. Literature from 1997 to 2017 was included.Study selectionArticles were included if they were written in English and described the implementation of a patient contract by a health care provider for the management of a chronic condition. Articles had to present an outcome as a result of using the contract or an intervention that included the contract.SynthesisOf the 7528 articles found in the original search, 76 met the inclusion criteria for the final review. Multiple study types were included. Extensive variety in contract elements, target populations, clinical settings, and cointerventions was found. Purposes for initiating contracts included behaviour change and skill development, including goal development and problem solving; altering beliefs and knowledge, including motivation and perceived self-efficacy; improving interpersonal relationships and role clarification; improving quality and process of chronic care; and altering objective and subjective health indices. How contracts were developed, implemented, and assessed was inconsistently described.ConclusionMore research is required to determine whether the use of contracts is accomplishing their intended purposes. Questions remain regarding their rationale, development, and implementation.