YTH domain-containing 2 (YTHDC2) is known to be an important regulator for RNA metabolism. Here, we show that YTHDC2 is essential for breast cancer tumorigenesis and metastasis. We examined YTHDC2 ...expression levels by immunohistochemistry in human breast tumor tissues from 99 patients and found a significantly positive correlation between the YTHDC2 expression level and the tumor stage. We established YTHDC2-knocked-down cell lines using four breast cancer cell lines with different subtypes. Knockdown of YTHDC2 attenuated the sphere-forming and the metastatic ability of breast cancer cells. Although stemness and EMT markers, such as SOX2, c-MYC, and NANOG, were downregulated in several YTHDC2-knocked-down breast cancer cells, a common target gene of YTHDC2 in breast cancer cells was not identified. These findings suggest that while YTHDC2 is involved in malignant progression of breast cancers, the mechanism by which YTHDC2 regulates those phenotypes is different between subtypes of breast cancers.
In clinical practice, drains had been routinely used for reducing seroma formation after breast surgery. However, an optimal timing to remove drains does not identify yet.
This study aimed to compare ...the clinical outcome, such as seroma formation, surgical site infection (SSI), and a length of hospital stay between early removal and late removal. A systematic review was performed using PubMed, MEDLINE, and the Cochrane Library. Breast cancer patients who received surgery using drains were eligible. Those parameters were compared between early vs late removal.
Eleven studies included in this meta-analysis. Seroma formation in the early removal group was significantly higher than the one in the late removal group (RR = 1.58: 95%CI 1.25-2.01, P = 0.0001), meanwhile no significant difference was found among the groups for SSI (RR = 0.82: 95%CI 0.51-1.31, P= 0.40). A length of hospital stay in the early removal group was also significantly shorter than late removal (RR -3.31: 95%CI -5.13-1.49, P = 0.0004).
Seroma formation was significantly higher in patients who had early drain removal. Conversely, SSI incidence was low, and early removal did not increase SSI incidence. In conclusion, early drain removal has no proved clinical benefit in these settings besides reduction of hospital stays.
Human endoplasmic reticulum oxidoreductin 1‐α (hERO1‐α) is an oxidizing enzyme that exists in the endoplasmic reticulum and its expression is augmented under hypoxia. It regulates a redox state of ...various kinds of protein through reoxidation of “client” protein disulfide isomerase. Interestingly, although the expression of hERO1‐α in normal tissues was comparatively limited, various types of cancer cells expressed it in large amounts. Therefore, we examined the role of ERO1‐α in tumor growth using murine breast cancer line 4T1 and found that knockdown of murine ERO1‐α inhibited in vivo tumor growth and decreased lung metastasis compared with wild‐type 4T1. Moreover, we investigated the relationship between expression of hERO1‐α and prognosis in breast cancer patients. Seventy‐one patients with breast cancer who underwent surgery between 2005 and 2006 in Sapporo Medical University Hospital (Sapporo, Japan) were analyzed in this study. Significant differences were found between the hERO1‐α‐positive group (n = 33) and hERO1‐α‐negative group (n = 38) in nuclear grade (P < 0.001) and intrinsic subtype (P = 0.021) in univariate analysis. More importantly, in multivariate analysis of disease‐free survival by Cox regression, expression of hERO1‐α was the only independent prognosis factor (P = 0.035). Finally, in univariate survival analysis, patients positive for hERO1‐α had significantly shorter disease‐free survival and overall survival than those patients negative for hERO1‐α. These findings indicate that the expression of hERO1‐α in cancer cells is associated with poorer prognosis and thus can be a prognostic factor for patients with breast cancer.
CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." There are still controversial reports questioning the association between
genotype ...and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of
genotype on tamoxifen therapy.
We enrolled 279 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen. We prospectively investigated the effects of allelic variants of
on Ki-67 response, pathological response, and hot flushes.
Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (
= 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor-positive cells in breast cancer tissues were significantly associated with Ki-67 response (
= 0.0076 and 0.0023, respectively). Although
variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (
= 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).
This is the first prospective study evaluating the relationship between
variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in
is a key predictor for the response to tamoxifen in patients with breast cancer.
.
A 62-year-old woman who underwent surgery to treat pancreatic cancer provided written, informed consent to undergo adjuvant therapy with gemcitabine, tegafur, and uracil. However, this was stopped ...after only 14 days due to Grade 4 neutropenia. She was then started on vaccine therapy with Survivin 2B peptide (SVN-2B) including IFA and INF-α. Although metastatic lung tumors were identified and resected at 82 months after surgery, the patient has remained free of new or relapsed disease for 12 years thereafter. Tetramer and ELISPOT assays revealed the continuous circulation of SVN-2B-restricted cytotoxic T-lymphocytes (CTLs) in her peripheral blood, and CTL clones had specific activity for SVN-2B at 12 years after surgery. The adverse effects of the peptide vaccination were tolerable and comprised low-grade headache, nausea, and fatigue. A prognosis beyond 10 years in the face of pancreatic cancer with distant metastasis is extremely rare. This experience might indicate the value of cancer vaccination therapy.
Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual ...response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen.
We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study.
The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the scoring system based on the genotypes of the three SNPs, patients with higher scores showed significantly higher after/before ratio of Ki-67 compared to those with lower scores (P = 1.8 x 10-12), suggesting the cumulative effect of the three SNPs.
We identified three novel loci, which could be associated with clinical response to tamoxifen. These findings provide new insights into personalized hormonal therapy for the patients with breast cancer.
Fine-needle aspiration (FNA) is commonly used as a preoperative assessment to diagnose thyroid cancer. However, misdiagnosis of malignancy by FNA is not rare, even if image examination suggests the ...possibility of thyroid cancer. In the present study, the clinicopathological factors of patients whose preoperative FNA examination had not led to a diagnosis of thyroid cancer were examined. In total, 125 patients with thyroid cancer who underwent FNA and surgery (total thyroidectomy, subtotal thyroidectomy or hemithyroidectomy) at the Department of Surgery, Surgical Oncology and Science of the Sapporo Medical University Hospital between 2006 and 2013 were retrospectively analyzed. The patients were divided into two groups: Group A, malignancy determined by FNA, and group B, no malignancy. The groups were then compared by gender, age, tumor size, stage, tumor stage, lymph node metastasis, histology, surgical procedure methods, presence or absence of calcification and thyroglobulin levels. The mean age of the patients in group A (5 males and 59 females) was 53.0 years. The mean age in group B (11 males and 49 females) was 54.2 years. The mean tumor size in both groups was 1.6 cm. The mean thyroglobulin levels were 82.7 ng/ml in Group A and 525.5 ng/ml in group B. There were also significant differences between the groups for tumor stage (P=0.046), histological type (P=0.024) and thyroglobulin levels (P=0.035). The results of the present study suggested that it may be difficult to diagnose thyroid cancer by FNA in cases with non-papillary carcinoma and higher thyroglobulin levels.
Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have ...been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.
Synchronous Paget disease of the breast and axilla Kobayashi, Keiju, MD; Sumikawa, Yasuyuki, MD, PhD; Kikuchi, Yumiko, MD ...
Journal of the American Academy of Dermatology,
01/2015, Volume:
72, Issue:
1
Journal Article
PDF
