CTLA4 expression profiles and their association with clinical outcomes of breast cancer: a systemic review

Purpose@#The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. @*Methods@#We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. @*Results@#CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. @*Conclusion@#This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial / 한국유방암학회지

Purpose@#Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. @*Methods@#The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Overexpression of FRAT1 protein is closely related to triple-negative breast cancer

Purpose@#Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. @*Methods@#First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. @*Results@#The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. @*Conclusion@#FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines

Purpose@#Papillary thyroid cancer (PTC) has a high incidence of BRAF V600E mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAF V600E mutation status in patients with PTC. We investigated how a selective inhibitor of BRAF V600E PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. @*Methods@#Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. @*Results@#Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/ M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colonystimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. @*Conclusion@#PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF V600E mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

Postthyroidectomy obesity in a Korean population: does the extent of surgery matter?

PURPOSE: The purpose of this study was to investigate the prevalence of postthyroidectomy obesity, and the relationship between the extent of thyroidectomy and obesity. METHODS: A survey conducted at an outpatient clinic from June to October 2014 and retrospective charts for patients undergoing thyroidectomy at Konkuk University Medical Centers from June 2009 to December 2013 were reviewed. We compared clinical characteristics and pre- and postoperative obesity-related factors in 227 patients who underwent total thyroidectomy or lobectomy. RESULTS: Patients included 39 males and 188 females with a mean age of 46.0 ± 11.0 years; the mean follow-up period was 23.9 ± 16.7 months, and 90 of the 227 patients showed postthyroidectomy obesity. In effect of operative extent on postoperative obesity, patients who underwent TT (48.2 years) than those who underwent lobectomy (43.4 years). TT group had longer follow-up and the frequency of menopause was higher than in the lobectomy group. No differences in postthyroidectomy obesity, body weight change, or body mass index (BMI), change among 2 groups. The predictors of postthyroidectomy obesity were older age, female, heavy alcohol consumption (P = 0.029), higher preoperative BMI (P < 0.001), larger postoperative weight gain (P = 0.024), and larger BMI change. However, the extent of thyroidectomy did not affect postthyroidectomy obesity. Preoperative BMI (P < 0.001) and heavy alcohol consumption (P = 0.03) were independent factors of postthyroidectomy obesity. CONCLUSION: The extent of thyroidectomy does not affect postthyroidectomy obesity. Preoperative BMI and heavy alcohol consumption are risk factors for postthyroidectomy obesity. Studies are needed to suggest preoperative life style modification to prevent postthyroidectomy obesity.

Selective B-RAF V600E Inhibitor PLX4032 Inhibits the Growth of Breast Cancer Cell Lines through Cell Cycle Arrest

PURPOSE: Breast cancer is the most common invasive cancer and the second common cause of death among women worldwide. Many researchers have focused on the effective treatment of advanced breast cancer using new drugs. Herein, we analyzed whether PLX4032, a B-RAF V600E inhibitor, could be used as a novel treatment for advanced breast cancer. METHODS: Two breast cancer cell lines, MCF7 and MDA-MB-231, were treated with the selective B-Raf inhibitor PLX4032 under adherent culture conditions and the effects of PLX4032 on cell growth, cell cycle duration, apoptosis and cell cycle related genes expression were evaluated. RESULTS: We found that PLX4032 dose-dependently inhibited cell growth in both cell lines through cell cycle arrest at phase G0/G1. However, PLX4032 treatment did not have a significant effect on cell apoptosis. In addition, CCNA2 gene expression was significantly decreased in the MCF7 cells in a dose-dependent manner. CONCLUSION: Our data demonstrated that treatment of breast cancer with PLX4032 could inhibit proliferation through cell cycle arrest. Therefore, PLX4032 might be a novel anticancer drug that can be used in the treatment of advanced breast cancer.

Feasibility of Hand-Assisted Laparoscopic Surgery as Compared to Open Surgery for Sigmoid Colon Cancer: A Case-Controlled Study

PURPOSE: The aim of this study was to evaluate short-term clinical outcomes by comparing hand-assisted laparoscopic surgery (HALS) with open surgery for sigmoid colon cancer. METHODS: Twenty-six patients who underwent a hand-assisted laparoscopic anterior resection (HAL-AR group) and 52 patients who underwent a conventional open anterior resection during the same period were enrolled (open group) in this study with a case-controlled design. RESULTS: Pathologic parameters were similar between the two groups. The incidences of immediate postoperative leukocytosis were 38.5% in the HAL-AR group and 69.2% in the open group (P = 0.009). There were no significant differences between the two groups as to leukocyte count, hemoglobin, and hematocrits (P = 0.758, P = 0.383, and P = 0.285, respectively). Of the postoperative recovery indicators, first flatus, sips of water and soft diet started on postoperative days 3, 5, 7 in the HALS group and on days 4, 5, 6 in the open group showed statistical significance (P = 0.021, P = 0.259, and P = 0.174, respectively). Administration of additional pain killers was needed for 1.2 days in the HAL-AR group and 2.4 days in the open group (P = 0.002). No significant differences in the durations of hospital stay and the rates of postoperative complications were noted, and no postoperative mortality was encountered in either group. CONCLUSION: The patients with sigmoid colon cancer who underwent a HAL-AR had a lower incidence of postoperative leukocytosis, less administration of pain killers, and faster first flatus than those who underwent open surgery. Clinical outcomes for patients' recovery and pathology status were similar between the two groups. Therefore, a HAL-AR for sigmoid colon cancer is feasible and has the same benefit as minimally invasive surgery.

Outcomes of Early Liver Transplantation in a Hospital That Is Starting to Perform Liver Transplantation / 대한이식학회지

BACKGROUND: In Korea, the number of liver transplantation (LT) center is still changing. Many more centers are performing liver transplantations than that during the past decades. But several centers have stopped liver transplantation, while some centers have newly started performing liver transplantation. We present our initial experience in a newly built center as an example for any center that is considering performing LT. METHODS: A total of 33 consecutive adult LTs that were performed from June 2006 to October 2009 were analyzed by comparing the first 11 living donor liver transplants (LDLTs) performed with the help of an outside experienced team (group 2) with the second 11 LDLTs (group 3) and the 11 deceased donor liver transplantations (DDLTs) cases (group 1) that were independently performed in our center. RESULTS: There was no operative mortality for the donors and there were two operative mortalities for the recipients. During a mean follow-up of 27.1 months (range: 2 days~61 months), there were two cases of late mortality for the recipients. There were no re-operations and no major complications for the donors. The warm ischemic time was significantly longer in group 1 than that in groups 2 and 3. Otherwise, there was no significant difference in the operative outcomes among the three groups. CONCLUSIONS: Thorough preparation and the valuable assistance of an experienced liver transplantation team at the beginning can facilitate a more rapid learning curve and bring about good outcomes even in a small, newly established institution.

Two Cases of the Cavernous Hemangioma of the Scrotum / 대한비뇨기과학회지

Cavernous hemangioma of the scrotum is a rare tumor with only 36 cases having previously been reported in literature and one case in Korea. We would like to add two cases of cavernous hemangioma of the scrotum with review of literature

Clinical Observation on Injuries of Genitourinary Tract / 대한비뇨기과학회지

A clinical observation was made on the injuries of genitourinary tract of the in-patient in the Department of Urology, Capital Armed Forces General Hospital during the period from January, 1974. to December, 1979. The results were as follows: 1) Of 1524 cases hospitalized, 184 cases were injuries of genitourinary tract giving a rate of 12.1%. 2) The most favorable age was in from 20 to 29 years for 65.8%. The sex ratio, male to female, was 13.2:1. 3) The kidney was involved most frequently in 30.9%, and the next was external genitalia in 28.9 %, the urethra in 21.1%, the bladder in 17.6% and the ureter in 1.5%. 4) Traffic accident was the most frequently in 30.9%, and the next was external genitalia in 28.9%. All 3 ureteral injuries were caused by gunshot. The kick or blow was the most frequent cause of injuries to the bladder(41.7%) and external genitalia (45.8%). 5) For the treatment of renal injuries, expectant management was performed in 43cases and operation in 20 cases. 6) Among 36 bladder injuries, intraperitoneal rupture in 16 cases was close to extraperitoneal rupture in 15 cases. The rests were contusion in 3 cases and vesicovaginal fistula in 2 cases. 7) The bulbous portion in 24 cases was involved most frequently in urethral injury, the next was membranous portion in 18 cases and the pendulous portion in only 1 case.

Clinical Observation on Undescended Testes / 대한비뇨기과학회지

A clinical observation was made on 50 cases of undescended testes of the in-patient in the Department of Urology, Capital Armed Forces General Hospital during the period from January, 1977 to December, 1976. The results were as follows: 1) Age distribution varies from 3 to 32 years and 21 cases (42%) were between 21 and 25 years old 2) Bilateral undescended testes were found in 7 cases, right in 28 cases and left in 15 cases 3) Of the 67 undescended testes, most popular location was inguinal type in 39 testes (68.4%) 4) Hormonal therapy was done on 8 cases (15 testes) but only 2 cases of bilateral type responded with partial descent. 5) Orchiopexy was performed on 35 testes (61. 4%), orchiectomy on 21 testes (36.8%) and 1 case (1.8%) was confirmed as monorchism on exploration. 6) Of the several methods of orchiopexy, dartos pouch method revealed high success rate (88. 5%). 7) In the histopathologic findings of testicular biopsies, there were presented numerous spermatogonia, not shown degenerative changes of seminiferous tubules, basement membrane and stroma, up to the age of 5, there were spermatogonia occasionally, atrophic findings of seminiferous tubules, thickening of basement membrane and widening of stroma.

A Case of Wilms' Tumor / 대한비뇨기과학회지

Wilms's tumor is a malignant renal parenchymal neoplasm. This tumor is most frequently discovered by palpable abdominal mass, while only total gross hematuria is not common in subjective symptom. We have experienced a four year-old girl complaining total gross hematuria and could not define preoperative diagnosis by clinical, radiological and laboratory findings. After operation, Wilms's tumor was confirmed on pathology.