The Efficacy of Time Perspective Therapy in Reducing Symptoms of Post-traumatic Stress, Anxiety, and Depression in Females with Breast Cancer

Background: Breast cancer is the biggest risk factor that endangers women's health. It is considered the highest stress-causing disease due to the unpleasant effects of disease on different aspects of patients’ life. Breast cancer is commonly associated with the symptoms of post-traumatic stress and its comorbidities such as anxiety and depression. It appears that time perspective therapy (TPT), as a new psychological treatment, can reduce the symptoms of post-traumatic stress, anxiety, and depression in females with breast cancer. Methods: This is a randomized controlled trial conducted from February to September 2019. A total of 30 patients with breast cancer were selected through a convenience sampling technique and were randomly divided into the control and treatment groups. The latter group attended 6-week sessions (each session lasted 90 minutes long) to receive TPT. To conduct pretest and posttest, all participants in the two groups were asked to fill out the following questionnaires: (1) Zimbardo Time Perspective Inventory (ZTPI); (2) The Post-traumatic Stress Disorder Checklist (PCL); (3) Beck Anxiety Inventory (BAI); and (4) the second version of Beck Depression Inventory (BDI-II). The analysis of covariance (ANCOVA) was used to evaluate the effects of treatment. A P-value smaller than 0.05 was considered significant. Results: Data analysis of 28 patients from the experimental and control groups showed that TPT significantly reduced the symptoms of post-traumatic stress, anxiety, and depression in the treatment group (P < 0.001 for symptoms of post-traumatic stress and anxiety, and P = 0.002 for depression). Such a difference was not seen in the control group. Conclusions: TPT may be an effective approach to reduce symptoms of post-traumatic stress, anxiety, and depression in Iranian women with breast cancer. Further investigations are required to confirm these findings, which may in turn help heath care professionals use TPT to promote the mental health of females with breast cancer.

Effect of 5'-fluoro-2'-deoxycytidine, 5-azacytidine, and 5-aza-2'–deoxycytidine on DNA Methyltransferase 1, CIP/KIP Family, and INK4a/ARF in Colon Cancer HCT-116 Cell Line

Background: Cyclin-dependent kinase inhibitors (CKIs) are the negative regulator of cell cycle progression, which inhibits cyclin-cdk complexes, resulting in cell cycle arrest. Recently, we evaluated the effect of 5-Aza-CdR on DNMT1 gene expression in the WCH-17 hepatocellular carcinoma (HCC) cell line. Objectives: The current study was designed to analyze the effects of 5-aza-2'–deoxycytidine (5-Aza-CdR, decitabine), 5-azacytidine (5-AzaC, vidaza), and 5'-fluoro-2'-deoxycytidine (FdCyd) on INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 gene expression, apoptosis induction, and cell growth inhibition in colon cancer HCT-116 cell line. Methods: The colon cancer HCT-116 cell line was treated with 5-azaC, 5-Aza-CdR, and FdCyd at 24 and 48h. To determine colon cancer HCT-116 cell viability, cell apoptosis, and the relative expression level of the INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 genes, MTT assay, flow cytometry, and qRT-PCR were done, respectively. Results: 5-azaC, 5-Aza-CdR, and FdCyd significantly inhibited colon cancer HCT-116 cell growth and induced apoptosis. Besides, they significantly increased CIP/KIP (p21CIP1, p27KIP1, and p57KIP2) and INK4 (p14ARF, p15INK4b, and p16INK4a) and decreased DNMT1 gene expression. Besides, minimal and maximal apoptosis were seen in the groups treated with FdCyd and 5-Aza-CdR, respectively. The IC50 for CAF for FdCyd was 1.72 ± 0.23 and 1.63 ± 0.21μM at 24 and 48h, respectively. The IC50 for CAF for 5-AzaC was 2.18 ± 0.33 and 1.98 ± 0.29 μM at 24 and 48h, respectively. The IC50 for CAF for 5-Aza-CdR was 4.08 ± 0.61 and 3.18 ± 0.50 μM at 24 and 48h, respectively. Conclusions: The 5-azac, 5-Aza-CdR, and FdCyd can reactivate the INK4a/ARF and CIP/KIP families through inhibition of DNMT1 activity.

Metastatic Breast Signet-Ring Cell Carcinoma from a Colonic Primary: Review of a Rare Case Report

Introduction: Colonic signet-ring cell carcinoma is a distinctive rare subtype of adenocarcinoma with a predilection for early metastasis. Among the rare extramammary metastatic adenocarcinomas to the breast, colonic signet-ring cell carcinomas constitute a small percentage. The distinction of a primary from a secondary breast signet ring cell carcinoma is indispensable since it may result in different therapeutic approaches. Here we presented a rare case of metastatic breast signet-ring cell carcinoma from a rectal origin and review its distinctive histopathologic features. Case Presentation: A 37-year-old woman presented with a breast mass 3 months after undergoing low anterior resection surgery to remove a rectal mass, diagnosed as signet ring cell carcinoma. Histopathologic examination of the core needle breast mass biopsy revealed tumor cells with signet-ring cell cytomorphology. The performed immunohistochemistry confirmed carcinoma of colonic origin. Conclusions: Colorectal signet-ring cell carcinoma is a rare and aggressive tumor. Its metastatic spread is most seen in the intra-abdominal area, with seldom reported cases of breast metastasis. Histologically, it can mimic a primary breast carcinoma, especially if no prior history of colonic origin exists. Accurate diagnosis is important since these 2 entities carry different therapeutic management. Proper immunophenotyping, obtaining a thorough clinical history and imaging studies facilitate a correct diagnosis.

Malignant Melanoma Presenting as a Parotid Mass in a Middle-aged Woman with Metastasis to the Breast

Introduction: Malignant melanomas of the parotid gland are relatively uncommon and usually seen as metastases from cutaneous or mucous sites of the head and neck region. Some malignant melanomas may metastasize before they regress. Therefore, identifying the primary origin of metastatic melanoma is sometimes difficult. Furthermore, metastasis to the breast from an extramammary site is uncommon and challenging. It may present as a well-defined rounded mass that histopathologically mimics the various architecture and cellular phenotypes. In addition, the immunohistochemical stains of some metastatic melanomas are equivocal and challenging. Case Presentation: We presented a case of parotid gland malignant melanoma in a 42-year-old woman with metastasis to the breast in a short interval. Biopsy of parotid and breast lesions showed loss of immune-reactivity for several melanoma markers and was initially considered as malignant peripheral nerve sheath tumor and primary breast tumor, respectively. Conclusions: This case highlights the importance of obtaining past clinical history in surgical pathology cases to make a correct diagnosis. It also enhances our understanding regarding malignant melanoma as a mysterious tumor with various morphology and immunophenotype.

Empowerment of Women to Provide Home-based Supportive and Palliative Care for Patients with Cancer: Participatory Action Research Protocol

Background: Determining the needs and challenges of women, who care for patients with cancer and providing appropriate strategies to empower them in the design and implementation of appropriate change programs pave the way for the promotion of these women's health and empowerment. Objectives: This study aims at identifying the needs and challenges of women and developing a program to empower women, who care for patients with cancer. Methods: The present study is based on a participatory action research approach and uses the Kemmis and McTaggart model. The participatory action research of this study will be in 4 phases of planning, action, observation, and reflection. In the planning phase, the needs and challenges of female caregivers are examined from the perspective of women and the health team and, then, women's empowerment strategies in providing home-based supportive and palliative care for patients with cancer are determined, using the results of the qualitative phase and review of the literature by using the decision matrix. In the action phase, the selected strategies are implemented with the help of process owners. In the observation phase, combining different methods, data will be collected to measure the results of change. Finally, in the reflection phase, the results of the implementation of the strategies are evaluated and this cycle continues until the intended results are achieved. Discussion: Empowerment of the women, who care for patients with cancer requires awareness, motivation, and active participation of women and the health team. As many cultural and social factors affect the health and participation of these women, participatory research can involve them in promoting their health.

Assessment of Breast Cancer Immunohistochemical Properties with Demographics and Pathological Features; A Retrospective Study

Background: Breast cancer is considered the most common malignant disease in the female population. It is known as an emerging epidemy with a great burden on women's health, which can be associated with poor outcomes. Some factors including histological type, immunohistochemistry (IHC), tumor grade, and tumor size can have effects on breast cancer. Objectives: This study aimed at assessing the effects of mentioned factors on IHC type of breast cancer. Methods: This retrospective cross-sectional study was conducted on 142 patients, who were referred to one of the referral centers for breast cancer in Mashhad. Information including age, histological type, familial history, menopause status, tumor grade, tumor size, and IHC properties was collected from the patient’s medical records. Allred score was used for reporting hormonal status. The data were analyzed by version 26 of SPSS software. Results: The mean age of patient was 50.2 ± 12.7. The frequency of luminal A and luminal B type was calculated as 29.7 and 18.9%, respectively. In addition, triple-negative IHC type has a prevalence of 24.3% and HER2 had a prevalence of 27%. There were no significant differences between age (P = 0.34), familial history (P = 0.42), menopause (P = 0.36), histological type (invasive: P = 0.11, in situ: P = 0.45), and IHC properties. However, tumor diameter (P = 0.0001) and tumor grading (P = 0.002) had significant association with IHC properties. Conclusions: Factors including tumor size and pathological grade can have effects on the gene expression properties of breast cancers. Luminal IHC type A is more common in breast cancer and is associated with better outcomes. However, age, histological type, familial history, and menopause status had no effects on the IHC properties of breast cancer.

Overexpression of GABRP Gene in Triple Negative Breast Cancer: Molecular Mechanisms and Interpretation

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease that characterized by aggressiveness features with increased metastasis and poor clinical prognosis. However, the molecular mechanisms underlying this highly malignant phenotype are still poorly understood. It has been well documented that the dysregulation of neural genes is profoundly implicated in cancer development and metastasis. Objectives: In the present study, the expression level of GABA receptor π subunit (GABRP) as the most up-regulated gene in TNBC and a hub node in the co-expression network were investigated. Methods: In this study, the importance of GABRP as the most up-regulated gene in TNBC was discovered through integrative analysis of multiple microarray expression datasets, containing about 1000 samples. Furthermore, the co-expression network analysis was constructed based on the up-regulated genes. Quantitative Real‐time polymerase chain reaction (qRT-PCR) was used to evaluate of the GABRP expression in 50 TNBC compared to 33 non-TNBC tumors. Results: According to the bioinformatics analysis, GABRP occupies a key position in the co-expression network which is mainly enriched in the nervous systems development. The qRT-PCR results indicated that up-regulation of GABRP was highly concordant with integrative analysis findings. Moreover, the receiver operating characteristic (ROC) curve analysis revealed that GABRP can be a potential biomarker to distinguish TNBC from non-TNBC samples. Conclusions: Our study revealed that up-regulation of GABRP is among the most remarkable molecular signature in TNBC and may play a critical role in tumorigenesis. The results may provide a deeper insight into molecular mechanisms underlying the brain metastasis in TNBC tumors and propose the potential targets for therapeutic interventions.

Diagnostic Value of Intraoperative Frozen Section in Breast-Conserving Surgery: A Systematic Review and Meta-analysis

Context: According to previous studies, using the frozen section procedure during breast surgery reduces the rate of error and the need for re-surgery. We aimed at performing a comprehensive systematic review and meta-analysis to provide reliable evidence on the diagnostic value of frozen section procedures in breast-conserving surgery (BCS). Data Sources: A thorough search was performed in PubMed, Embase, Cochrane Library, and Web of Science databases for human diagnostic studies that used the frozen section in BCS. Meta-analyses were done to find the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Study Selection: Human diagnostic studies used the frozen section in breast-conserving surgery and studies that reported the sensitivity and specificity of the frozen section in BCS or contained data that could be calculated the desired parameters were selected for this meta-analysis. Data Extraction: Assessment of studies quality was done and data was extracted from included papers. Then, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of included papers. Results: Thirty-five papers were entered into our study. The meta-analysis indicated the high sensitivity (83.47, 95%CI 79.61 - 87.32) and specificity (99.29, 95%CI 98.89 - 99.68) for the frozen section in BCS, which resulted in an accuracy of 93.77 (95%CI 92.45 - 95.10). We also found a significant PPV (93.26, 95%CI 91.25 - 95.27), NPV (92.17, 95%CI 90.22 - 94.11), PLR (7.99, 95%CI 6.01 - 9.96), and NLR (0.18, 95%CI 0.14 - 0.23). Conclusions: The findings showed that intraoperative frozen section analysis has high sensitivity and specificity for evaluating lumpectomy margins in patients with early-stage breast cancer and significantly reduces the need for re-operation. Accordingly, re-operation costs are not imposed on the patient and reduce the anxiety of the patients.

Quercetin Enhances the Suppressive Effects of Doxorubicin on the Migration of MDA-MB-231 Breast Cancer Cell Line

Background: Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities. Objectives: This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB-231 breast cancer cell line. Methods: The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes. Results: The combination of 50 µM of que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone. Conclusions: Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy.