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1.
J Lesbian Stud ; : 1-20, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38132823

ABSTRACT

Drawing on queer of color critique, this paper uses mixed methods including participant observation, interviews, visual and textual analysis, and photovoice to interrogate sex workers' queer creative practices. Building upon the larger oeuvre of sex working artists, contemporary sex working artists in Los Angeles utilizes queer creativity to thwart hegemonic readings of sex work. Performances at two activist fundraisers drew on the themes and esthetics of sex work to counter mainstream narratives about sex work and workers, and to interrupt their objectification. The cover and graphics of a sex worker zine push back against dominant narratives about sex workers and the power structures that suppress sex worker self-representation. Photovoice methodology allowed sex workers to counteract objectification by telling their own stories. In their creative products, sex workers show how "queer" is a praxis of sex and gender disruption, rather than a simple identity category signaling non-heterosexuality, challenging homonormativity in addition to heteronormativity.

2.
Article in English | WPRIM (Western Pacific) | ID: wpr-1002172

ABSTRACT

Desmoplastic Spitz nevus is a rare variant of Spitz nevus characterized by predominantly spindle-shaped or epithelioid nevus cells within the fibrotic stroma that can be confused with fibrous lesions. A 43-year-old woman presented with a 1-cm-sized dome-shaped papule on the dorsum of her left foot. The lesion showed histopathological features of a desmoplastic Spitz nevus with structures that resemble adenoma. Immunohistochemical staining was positive for S-100 protein, Melan-A, and SOX-10. Herein, we report this case because desmoplastic Spitz nevus is rare and can lead to confusion regarding the diagnosis of adnexal neoplasms.

3.
Cancer Research and Treatment ; : 1198-1209, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-999826

ABSTRACT

Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

4.
J Bone Oncol ; 32: 100409, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35024328

ABSTRACT

Aromatase inhibitor treatment in breast cancer is associated with accelerated bone loss and an increased risk of fracture. Bisphosphonates (BPs) are the mainstay treatment of aromatase inhibitor-associated bone loss (AIBL), which might improve femoral bone at key locations prone to fracture. To test this hypothesis, we performed three-dimensional cortical bone mapping based on quantitative computed tomography (QCT) scans in postmenopausal women with early breast cancer who were receiving aromatase inhibitors. Data of subjects who had both baseline and at least one follow-up QCT at Severance Hospital (South Korea) between 2005 and 2015 were analyzed (BP users, n = 93; BP non-users, n = 203). After exclusion of BP users with low medication persistence (proportion of days covered: <50%), BP users and non-users were 1:1 matched (n = 54 for each group) in terms of age, lumbar spine volumetric bone mineral density (LSvBMD), femoral neck areal BMD (FNaBMD), and total hip areal BMD (THaBMD). During a median follow-up of 2.1 years, BP use attenuated bone loss in LSvBMD (+7.2% vs. -3.8%, p < 0.001), FNaBMD (+1.3% vs. -2.7%, p < 0.001), and THaBMD (-0.3% vs. -2.5%, p = 0.024). BP had a protective effect on cortical parameters of femoral bone: estimated cortical thickness (CTh) (+3.3% vs. + 0.1%, p = 0.007) and cortical mass surface density (CMSD, cortical mass per unit surface area was calculated by multiplying cortical BMD with CTh) (+3.4% vs. -0.3%, p < 0.001). CMSD increased by up to 15% at key locations such as the superior part of the femoral neck and greater trochanter. BP prevented the thinning of average CTh of the femoral neck (-1.4% vs. -6.1%, p < 0.001), particularly at the superior anterior quadrant of femoral neck (absolute difference: +12.8% point vs. non-users). Compared to BP non-users, BP users had improved cross-sectional moment of inertia (+4.4% vs. -0.7%, p = 0.001) and less increase in buckling ratio (+1.3% vs. + 7.5%, p < 0.001). In summary, BP use prevented cortical bone deficits observed in AIBL at key locations of the proximal femur.

5.
Yonsei Medical Journal ; : 158-165, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-919601

ABSTRACT

Purpose@#The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. @*Materials and Methods@#Intraabdominal transplant of cardiac allografts from BALB/c (H-2d ) donors to C57BL/6 (H-2b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. @*Results@#The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4 + FOXP3+ /CD4+ CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+ CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. @*Conclusion@#These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

6.
Yonsei Medical Journal ; : 137-148, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-875592

ABSTRACT

Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

7.
Journal of Breast Disease ; (2): 10-15, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-891322

ABSTRACT

Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.

8.
Journal of Breast Cancer ; : 183-195, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-891274

ABSTRACT

Purpose@#Nipple-sparing mastectomy (NSM) includes various techniques, including conventional or endoscopic mastectomies. Since the introduction of robot-assisted NSM (RANSM) in 2015, 2 main methods have been used: gasless and gas-inflated techniques. The aim of this study was to compare clinicopathologic characteristics, surgical outcomes, and postoperative complications between patients treated with gasless RANSM and those treated with gas-inflated RANSM. @*Methods@#We conducted a retrospective study of women who underwent gasless or gasinflated RANSM with immediate breast reconstruction between November 2016 and May 2019. The indications for RANSM were early breast cancer, interstitial mastopathy, or BRCA1/2 mutation carriers. Clinicopathologic characteristics, surgical outcomes, and postoperative complications were analyzed. The severity of complications was graded using the Clavien-Dindo system. @*Results@#A total of 58 RANSM procedures were performed in 46 women: 15 cases of gasless RANSM and 43 cases of gas-inflated RANSM. The proportion of node-negative disease was higher in the gas-inflated group (97.1%) than in the gasless group (69.2%, p = 0.016).Adjuvant radiotherapy was administered in 30.6% of the cases in the gasless group and only 5% of the cases in the gas-inflated group. Other clinicopathological factors were not significantly different between the groups. Regarding surgical outcomes, the initial incision was 1 cm longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.20 ± 1.05 cm; p = 0.002). The final incision was also longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.57 ± 1.07 cm; p = 0.040). Operation time, complication rate, and complication grade were not significantly different between the 2 groups. @*Conclusion@#In this study, there were no significant differences in surgical outcomes or postoperative complications between gasless and gas-inflated RANSM, except for a longer incision with the gasless technique. Both techniques are reasonable options for RANSM followed by immediate reconstruction.

9.
Article in English | WPRIM (Western Pacific) | ID: wpr-901311

ABSTRACT

Langerhans cell histiocytosis (LCH) is a rare condition that usually occurs in children and commonly affects the skeletal system. It is extremely rare in adults, especially in the clavicles. In this report, we describe a pathologically confirmed case of LCH in the clavicle of a 50-year-old male. We report various radiological findings, such as plain radiography, CT, MR, and PET-CT, along with a review of the literature.

10.
Journal of Breast Disease ; (2): 10-15, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-899026

ABSTRACT

Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.

11.
Journal of Breast Cancer ; : 183-195, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-898978

ABSTRACT

Purpose@#Nipple-sparing mastectomy (NSM) includes various techniques, including conventional or endoscopic mastectomies. Since the introduction of robot-assisted NSM (RANSM) in 2015, 2 main methods have been used: gasless and gas-inflated techniques. The aim of this study was to compare clinicopathologic characteristics, surgical outcomes, and postoperative complications between patients treated with gasless RANSM and those treated with gas-inflated RANSM. @*Methods@#We conducted a retrospective study of women who underwent gasless or gasinflated RANSM with immediate breast reconstruction between November 2016 and May 2019. The indications for RANSM were early breast cancer, interstitial mastopathy, or BRCA1/2 mutation carriers. Clinicopathologic characteristics, surgical outcomes, and postoperative complications were analyzed. The severity of complications was graded using the Clavien-Dindo system. @*Results@#A total of 58 RANSM procedures were performed in 46 women: 15 cases of gasless RANSM and 43 cases of gas-inflated RANSM. The proportion of node-negative disease was higher in the gas-inflated group (97.1%) than in the gasless group (69.2%, p = 0.016).Adjuvant radiotherapy was administered in 30.6% of the cases in the gasless group and only 5% of the cases in the gas-inflated group. Other clinicopathological factors were not significantly different between the groups. Regarding surgical outcomes, the initial incision was 1 cm longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.20 ± 1.05 cm; p = 0.002). The final incision was also longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.57 ± 1.07 cm; p = 0.040). Operation time, complication rate, and complication grade were not significantly different between the 2 groups. @*Conclusion@#In this study, there were no significant differences in surgical outcomes or postoperative complications between gasless and gas-inflated RANSM, except for a longer incision with the gasless technique. Both techniques are reasonable options for RANSM followed by immediate reconstruction.

12.
Article in English | WPRIM (Western Pacific) | ID: wpr-893607

ABSTRACT

Langerhans cell histiocytosis (LCH) is a rare condition that usually occurs in children and commonly affects the skeletal system. It is extremely rare in adults, especially in the clavicles. In this report, we describe a pathologically confirmed case of LCH in the clavicle of a 50-year-old male. We report various radiological findings, such as plain radiography, CT, MR, and PET-CT, along with a review of the literature.

13.
Article | WPRIM (Western Pacific) | ID: wpr-835994

ABSTRACT

Heterotopic ossification is the formation of extra-skeletal bone in the muscle and soft tissues, and an osteoma is a benign bone-forming tumor composed of compact or mature trabecular bone limited almost exclusively to the craniofacial bones. This paper reports an extremely rare case of heterotopic ossification mimicking an osteoma that occurred independently at the plantar side of the medial sesamoid bone. The patient was a 46-year-old male with a three-month history of pain and a hard mass on the plantar aspect of the left forefoot sole. After excising the lesion, the patient’s symptoms were relieved, and no pain or complications occurred. This paper discusses this exceedingly rare case of heterotopic ossification around the medial sesamoid bone with a review of the relevant literature.

14.
Article in English | WPRIM (Western Pacific) | ID: wpr-891660

ABSTRACT

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

15.
Article in English | WPRIM (Western Pacific) | ID: wpr-899364

ABSTRACT

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

16.
Article | WPRIM (Western Pacific) | ID: wpr-830494

ABSTRACT

Objective@#To examine the correlation between the Frontal Assessment Battery (FAB) test, which is used to assess the frontal lobe function, and anatomical lesions as well as the ability of the test to detect frontal lobe dysfunction. @*Methods@#Records of stroke patients undergoing a FAB test and Mini-Mental State Examination (MMSE) were retrospectively reviewed. The patients were divided into three groups according to the lesions determined by an imaging study: frontal lobe cortex lesions, frontal subcortical circuit lesions, and other lesions. The FAB scores of the three groups were compared using the Kruskal-Wallis test. The validity of the FAB test to detect frontal lobe dysfunction was assessed by a comparison with the Computerized Neuropsychological Function Test (CNT) using the Spearman correlation coefficient. The correlation coefficients between the FAB test and MMSE were analyzed further based on the MMSE cutoff score. @*Results@#Patients with frontal cortex lesions had significantly lower total and subtest scores according to the FAB test than the other patients. The FAB test correlated better with the CNT than the MMSE, particularly in the executive function and memory domains. A high MMSE score (r=0.435) indicated a lower correlation with the FAB test score than a low MMSE score (r=0.714). @*Conclusion@#The FAB test could differentiate frontal lobe lesions from others in stroke patients and showed a good correlation with the CNT. Moreover, the FAB test can be used in patients with high MMSE scores to detect frontal lobe dysfunction and determine the treatment strategies for stroke patients.

17.
Article in English | WPRIM (Western Pacific) | ID: wpr-811196

ABSTRACT

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system.METHODS: Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria.RESULTS: In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001).CONCLUSIONS: Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.


Subject(s)
Humans , Breast Neoplasms , Breast , Joints , Neoadjuvant Therapy , Prognosis
18.
Article in English | WPRIM (Western Pacific) | ID: wpr-766036

ABSTRACT

Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.


Subject(s)
Adult , Female , Humans , Biopsy , Colitis , Colitis, Ulcerative , Colon , Diagnosis , Diagnostic Errors , Lymphocytes , Lymphoma , Ulcer
19.
Immune Network ; : e11-2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-740217

ABSTRACT

During virus infection, T cells must be adapted to activation and lineage differentiation states via metabolic reprogramming. Whereas effector CD8⁺ T cells preferentially use glycolysis for their rapid proliferation, memory CD8⁺ T cells utilize oxidative phosphorylation for their homeostatic maintenance. Particularly, enhanced AMP-activated protein kinase (AMPK) activity promotes the memory T cell response through different pathways. However, the level of AMPK activation required for optimal memory T cell differentiation remains unclear. A new metformin derivative, IM156, formerly known as HL156A, has been reported to ameliorate various types of fibrosis and inhibit in vitro and in vivo tumors by inducing AMPK activation more potently than metformin. Here, we evaluated the in vivo effects of IM156 on antigen-specific CD8⁺ T cells during their effector and memory differentiation after acute lymphocytic choriomeningitis virus infection. Unexpectedly, our results showed that in vivo treatment of IM156 exacerbated the memory differentiation of virus-specific CD8⁺ T cells, resulting in an increase in short-lived effector cells but decrease in memory precursor effector cells. Thus, IM156 treatment impaired the function of virus-specific memory CD8⁺ T cells, indicating that excessive AMPK activation weakens memory T cell differentiation, thereby suppressing recall immune responses. This study suggests that metabolic reprogramming of antigen-specific CD8⁺ T cells by regulating the AMPK pathway should be carefully performed and managed to improve the efficacy of T cell vaccine.


Subject(s)
AMP-Activated Protein Kinases , Cell Differentiation , Fibrosis , Glycolysis , Immunologic Memory , In Vitro Techniques , Lymphocytic choriomeningitis virus , Lymphocytic Choriomeningitis , Memory , Metformin , Oxidative Phosphorylation , T-Lymphocytes
20.
Article in English | WPRIM (Western Pacific) | ID: wpr-763115

ABSTRACT

PURPOSE: Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent meta-analysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. MATERIALS AND METHODS: Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. RESULTS: Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). CONCLUSION: Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.


Subject(s)
Humans , Abdominal Pain , Alopecia , Anorexia , Appointments and Schedules , Breast Neoplasms , Breast , Cyclophosphamide , Diarrhea , Disease-Free Survival , Doxorubicin , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Dyspepsia , Febrile Neutropenia , Headache , Incidence , Mucositis , Muscle Weakness , Myalgia , Nausea
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