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1.
Surgeon ; 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38161142

RESUMEN

INTRODUCTION: Oncoplastic surgery is an important component of the management of breast cancer. As prognosis has improved, the need for proficient techniques to achieve disease eradication while maintaining cosmesis for naturally appearing breasts has gained importance. This study describes an easy-to-learn modified oncoplastic technique for patients undergoing breast-conserving treatment. DESCRIPTION OF THE TECHNIQUE: Tumor resection is performed through different peri-areolar, inframammary, or radial incisions. To reduce the size of the surgical defect created after tissue resection, an internal purse-string is performed parallel to the chest wall or base of the wound with subsequent staggering in three or more layers as needed, while maintaining the parallel orientation of the needle. This is followed by the creation and overlapping of internal breast tissue flaps that are rearranged to decrease the dead space with the aim of improving cosmesis. The redundant skin is removed for the skin envelope to maintain shape. The wound is closed in layers. We also describe steps in performing sentinel lymph node and tumor extraction through the same periareolar, inframammary, or radial incisions for tumors located in outer quadrants. Following closure, contour and projection of the breast were maintained without indentation or loss of projection, with a symmetrical appearance to the contralateral side. CONCLUSION: This simplified oncoplastic (MOLLER) technique can be easily learned and used by surgeons who treat cancer patients and have limited oncoplastic training. It uses basic known surgical principles to decrease the size of the defect created while minimizing the need for larger incisions/pedicles.

2.
Breast Cancer Res Treat ; 192(2): 369-373, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34988768

RESUMEN

INTRODUCTION: Breast cancer survivors are often prescribed medications for at least 5 years to reduce recurrence risk, yet some forego this treatment due to cost. We sought to elucidate the prevalence of this and the factors contributing to it. METHODS: The National Health Interview Survey (NHIS) is a population-based survey, representative of the civilian non-institutionalized US population, administered annually by the CDC. People diagnosed with breast cancer within the past 5 years surveyed in the 2018 NHIS formed the cohort of interest. RESULTS: Of the 24,858 breast cancer survivors surveyed, representing 244,607,304 in the population, 6.32% stated that they needed a prescription medicine within the past 12 months, but didn't get it filled because they couldn't afford it. Of those who had gotten a prescription within the past 12 months, 5.71, 5.94 and 7.48% had either skipped doses, taken less medication than prescribed, or delayed filling a prescription, respectively, to save money. 11.99% of people had done at least one of these, thereby foregoing treatment. On bivariate analyses, factors associated with foregoing treatment included age, race, education, family income, and insurance status (p < 0.001 for all). On multivariable analysis, age, race, family income, and insurance status were all independent predictors of foregoing treatment (p < 0.001 for all); education status was not significant in the model (p = 0.211). CONCLUSION: Roughly 12% of breast cancer survivors who are prescribed medications within the first 5 years of their diagnosis will forego treatment due to cost. Family income and insurance status are key modifiable drivers of this.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Cobertura del Seguro , Cumplimiento de la Medicación , Sobrevivientes
3.
BMC Cancer ; 22(1): 34, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983451

RESUMEN

INTRODUCTION: Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifications and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. The aim of this study is to elucidate the role of secretion of BMP-2 by TAMs in promoting microcalcifications of breast cancer through immunohistochemical staining and co-culturing of breast cancer cells with TAMs. METHODS: A total of 272 patients diagnosed with primary invasive breast cancer from January 2010 to January 2012 in the First Hospital of China Medical University were included in this study. Immunohistochemical staining of CD68 (marker of entire macrophages), CD168 (marker of the M2-like macrophages) and BMP-2 were performed on 4-µm tissue microarray (TMA) sections. Following induction, THP-1 cells were differentiated to M2-like TAMs and were then co-cultured with breast cancer cells (MCF-7). Calcifications and BMP-2 expression were analyzed by Alizarin Red S staining and western blot, respectively. RESULTS: Immunohistochemical analysis showed that the expression of CD168 was significantly increased in tissues with microcalcifications and was correlated with the expression of BMP-2 and poor prognosis. The formation of cellular microcalcifications and BMP-2 expression were significantly increased in MCF-7 cells co-cultured with TAMs compared with MCF-7 cells alone. CONCLUSIONS: These findings support the hypothesis that TAMs secrete BMP-2 to induce microcalcifications in breast cancer cells and influence prognosis via multiple pathways including BMP-2 and its downstream factors.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Neoplasias de la Mama/metabolismo , Calcinosis/genética , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Mama/metabolismo , Técnicas de Cocultivo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Pronóstico
4.
J Surg Res ; 277: 110-115, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35489215

RESUMEN

INTRODUCTION: Asian American women have lower breast cancer incidence and mortality than their non-Hispanic White (NHW) counterparts. We sought to determine whether differences in screening practices could explain, in part, the variation in breast cancer detection rate. METHODS: The 2015 National Health Interview Survey, an annual survey that is representative of the civilian, noninstitutionalized American population, was used to determine whether mammography usage was different between Asian and NHW women. Women ≥40 y of age who identified as either Asian or NHW were included. RESULTS: A total of 7990 women ≥40 y of age (6.12% Asian, 93.88% NHW), representing 53,275,420 women in the population, were included in our cohort of interest; 71.49% of Asian and 74.46% of NHW women reported having had a mammogram within the past 2 y (P = 0.324). Controlling for education, insurance, family income, marital status, and whether they were born in the United States, Asians were less likely to have had a mammogram within the past 2 y than their NHW counterparts (odds ratio = 0.68; 95% confidence interval: 0.46-0.99, P = 0.047). Of patients who had an abnormal mammogram, there was no difference in the biopsy rate (20.35% versus 25.97%, P = 0.4935) nor in the rate of cancer diagnosis among those who had a biopsy (7.70% versus 12.86%, P = 0.211) between Asian and NHW women, respectively. CONCLUSIONS: Our findings suggest that the lower breast cancer incidence among the Asian population may, in part, be explained by a lower screening mammography rate in this population.


Asunto(s)
Neoplasias de la Mama , Mamografía , Asiático , Neoplasias de la Mama/patología , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Estados Unidos/epidemiología
5.
J Drugs Dermatol ; 18(11): 1180-1182, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31741363

RESUMEN

Background: Significant advances have been made in using lasers and intense pulse light sources to treat common vascular lesions such as telangiectasias. However, the treatment of leg telangiectasia, specifically, is more challenging because it involves the clearing of smaller veins as well as the larger feeding veins. The latest guidelines recommend use of short wavelength pulse-dyed lasers (PDL) as an option to treat telangiectasia cases that are unresponsive to sclerotherapy. Methods: A 29-year-old white woman presented with persistent telangiectasia, with multiple telangiectasias ranging from 1 cm to 20 cm in size involving the dorsal feet and both ankles and legs, which developed 10 years prior, associated with paresthesia. Test spots were treated with a 585-nm pulsed dye laser with various energy settings, and treatment was performed at 5.5 J/cm2 with spot size 10 mm and 0.5ms pulse duration. Results: Near complete clearance was achieved 1 month after the single treatment without adverse effects. Optical coherence tomography (OCT) imaging demonstrated a reduction of cutaneous blood flow after treatment. Discussion: We report successful treatment despite using settings that were previously reported to lack efficacy. This treatment resulted in considerable improvement in aesthetics and symptomatology. Also, OCT confirmed decreased vascular flow and bulging. Conclusion: Our results suggest there is still much to learn about the use of PDL in treating telangiectasias of the lower extremities, and that the ideal parameters warrant further investigation. Moreover, the novel use of OCT in auxiliary imaging for identification of treatment spots, as well as monitoring response at a microvascular level, holds great potential for wider application. J Drugs Dermatol. 2019;18(11):1180-1182.


Asunto(s)
Láseres de Colorantes/uso terapéutico , Pierna/irrigación sanguínea , Terapia por Luz de Baja Intensidad , Telangiectasia/radioterapia , Adulto , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Tomografía de Coherencia Óptica
6.
Lasers Med Sci ; 34(2): 411-420, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30539405

RESUMEN

No consensus guidelines exist on the use of optical coherence tomography (OCT) for diagnosis of cutaneous melanoma. The objectives of this review are to provide a descriptive review of the literature on characteristics of cutaneous melanomas seen on high-definition OCT (HD-OCT), speckle variance OCT (SV-OCT), and conventional OCT and to compare their diagnostic ability with that of histopathology. A review of PubMed and Google Scholar identified all available literature on OCT in melanoma skin cancer that included all in vivo and ex vivo studies on human or human tissues and excluded all studies on non-human subjects or animal studies. Two hundred nine abstracts were considered for evaluation, 31 abstracts were selected for manuscript review, and 14 abstracts were included that met all criteria. Diagnoses of MIS and MM using HD-OCT and SV-OCT were consistently reported to correlate with histopathology. However, accuracy of diagnosis using conventional OCT varied. Most authors agreed that it was difficult to differentiate MM from benign nevi using conventional OCT. HD-OCT, SV-OCT, and conventional OCT show promise for visualizing cutaneous melanoma. The use of OCT in diagnosis of melanoma is rarely reported in the literature. There is a need to increase and standardize reporting of OCT for diagnosis of cutaneous melanoma.


Asunto(s)
Melanoma/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Humanos , Melanoma/diagnóstico , Melanoma/patología
9.
Oncol Lett ; 28(2): 366, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38933812

RESUMEN

Early breast cancer (EBC) is cancer that has not spread beyond the breast or the axillary lymph nodes. The present retrospective cohort study investigated the efficacy and safety of the Pingxiao capsule (PXC), which contains a formula of traditional Chinese herbs, as adjuvant therapy in patients with EBC in a single Chinese academic medical center. Patients with EBC who had received surgery and chemotherapy were analyzed and divided into the PXC and non-PXC groups. Disease-free survival (DFS) time, overall survival (OS) time, demographic characteristics and adverse events were examined. Kaplan-Meier survival curves were used to compare the differences in DFS and OS. A total of 371 participants with a median age of 54 years were included in this study. The median DFS time of all patients was 101 months. The overall DFS rate was 72.1% in the PXC group compared with 63.6% in the non-PXC group. For women with hormone receptor-negative tumors, the DFS rate in the PXC group was significantly higher than that in the non-PXC group, irrespective of node status. Adjuvant treatment with PXC for ≥3 months was associated with significantly longer median DFS time compared with that in the non-PXC group. In addition, the incidence of neutropenia rated to be grade 2 or higher was significantly lower in the PXC group compared with that in the control group, and a markedly, but non-significantly, lower prevalence of nausea was observed in PXC group (0 vs. 4.1%). In conclusion, PXC as an adjuvant therapy along with chemotherapy is associated with prolonged DFS times in patients with EBC when compared with chemotherapy alone. The therapeutic value of combined PXC and systemic chemotherapy should be further elucidated by rigorous prospective clinical trials.

10.
J Surg Educ ; 80(5): 689-696, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36933957

RESUMEN

INTRODUCTION: Surgery trainees spend their prime fertility years in training, which leads to delays in childbearing, accompanying infertility challenges, and high-risk pregnancies. Literature report of institutional support for fertility preservation (egg/sperm freezing) and treatment is lacking. The cost is particularly prohibitive while receiving a resident physician salary. This study aimed to assess availability of fertility resources and institutional coverage of fertility services to US General Surgery Residents (GSR) and Breast Fellows. METHODS: We composed and distributed a 26-question survey to GS residency and fellowship program directors nationwide to survey residents and fellows. Summary and descriptive statistics were tabulated, and categorical variables were analyzed using Pearson's chi square test. RESULTS: A total of 234 US surgical trainees (male n = 75, female n = 155, unreported n = 4) completed the survey. Total of 12 % of trainees reported having been counseled on family planning/fertility treatment during training, and only 5.1% were counseled on fertility preservation. Perceived lack of support from program (p = 0.027) and counseling of fertility preservation (p = 0.009) were significantly associated with female gender. A minority (12.5%) reported having insurance coverage for fertility preservation and 26% had coverage of fertility treatment. In addition, 2.6% respondents pursued fertility preservation while in training and 33% reported they would pursue fertility preservation if it was covered by insurance. CONCLUSIONS: Fertility preservation is rarely discussed in US General Surgery residency programs. The large majority of GSR lacks awareness of insurance coverage of fertility preservation and treatment. Strong efforts are necessary to improve fertility education for GSR and insurance coverage to meet trainee's needs.


Asunto(s)
Preservación de la Fertilidad , Internado y Residencia , Embarazo , Masculino , Humanos , Femenino , Estados Unidos , Preservación de la Fertilidad/psicología , Encuestas y Cuestionarios , Cobertura del Seguro , Mama
11.
Plast Reconstr Surg ; 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37699106

RESUMEN

BACKGROUND: Direct-to-implant (DTI) reconstruction has multiple advantages over a staged tissue expander (TE) approach. However, its use may be limited by concerns of increased complications. This study is the largest series to date comparing postoperative outcomes for DTI versus TE reconstruction in the prepectoral plane. METHODS: The authors retrospectively reviewed 348 patients that received 536 total immediate, prepectoral implant-based breast reconstructions between January 2018 and December 2021. The authors compared the presence of risk factors and the rate of six separate complications between patients that received DTI versus TE reconstruction up to one year after surgery. RESULTS: Of 348 patients, 147 (42%) and 201 (58%) underwent TE and DTI reconstruction (p=0.1813), respectively. Overall infection rate was 16.4% (n=57). DTI patients had a significantly greater incidence of wounds (p<0.0001), including minor (p<0.0011) and major wounds (p<0.0053). Significantly greater mastectomy resection weights were found for DTI patients that experienced any complication (p<0.0076), postoperative wounds (p<0.0001), and major wounds specifically (p<0.0035). Compared to medium thickness, extra-thick acellular dermal matrix (ADM) was associated with significantly increased rates of infection (p<0.0408) and wounds (p<0.0001). CONCLUSIONS: Prepectoral DTI reconstruction in patients with adequate flap perfusion may have comparable complication rates to staged TE reconstruction apart from a higher incidence of postoperative wounds. Greater mastectomy resection weights and thickness of ADM may specifically contribute to infectious and wound-healing complications. Prepectoral DTI reconstruction is encouraged in the patients with adequate flap perfusion and moderate to low mastectomy resection weights that desire comparable or smaller implant volumes.

12.
Proc (Bayl Univ Med Cent) ; 36(4): 501-509, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334077

RESUMEN

Introduction: Perioperative pain control is an important component of any plastic surgery practice. Due to the incorporation of Enhanced Recovery after Surgery (ERAS) protocols, reported pain level, opioid consumption, and hospital length of stay numbers have decreased significantly. This article provides an up-to-date review of current ERAS protocols in use, reviews individual aspects of ERAS protocols, and discusses future directions for the continual improvement of ERAS protocols and control of postoperative pain. ERAS components: ERAS protocols have proven to be excellent methods of decreasing patient pain, opioid consumption, and postanesthesia care unit (PACU) and/or inpatient length of stay. ERAS protocols have three phases: preoperative education and pre-habilitation, intraoperative anesthetic blocks, and a postoperative multimodal analgesia regimen. Intraoperative blocks consist of local anesthetic field blocks and a variety of regional blocks, with lidocaine or lidocaine cocktails. Various studies throughout the surgical literature have demonstrated the efficacy of these aspects and their relevance to the overall goal of decreasing patient pain, both in plastic surgery and other surgical fields. In addition to the individual ERAS phases, ERAS protocols have shown promise in both the inpatient and outpatient sectors of plastic surgery of the breast. Conclusion: ERAS protocols have repeatedly been shown to provide improved patient pain control, decreased hospital or PACU length of stay, decreased opioid use, and cost savings. Although protocols have most commonly been utilized in inpatient plastic surgery procedures of the breast, emerging evidence points towards similar efficacy when used in outpatient procedures. Furthermore, this review demonstrates the efficacy of local anesthetic blocks in controlling patient pain.

13.
JAMA Dermatol ; 158(3): 288-292, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35080592

RESUMEN

IMPORTANCE: Although there have been increased efforts in dermatologic research to improve representation of patient sex, race, and ethnicity, there are limited data evaluating resulting changes. OBJECTIVE: To characterize the diversity of participants in dermatologic clinical trials conducted in the US published from 2015 to 2020 pertaining to common dermatologic conditions affecting all patient demographic categories compared with findings from 2010-2015. EVIDENCE REVIEW: A systematic literature review through the PubMed database was conducted for randomized clinical trials published between July 1, 2015, and July 1, 2020, using keywords alopecia areata, acne, atopic dermatitis, lichen planus, psoriasis, seborrheic dermatitis, and vitiligo. Data collected included distribution of participant demographic characteristics, funding source, and journal type. Reflecting US Census data, studies were defined as unrepresentative of race and ethnicity if they included less than 20% ethnically or racially diverse participants or unrepresentative of sex if they included less than 45% women. Python was used for statistical analysis by χ2 tests or Fisher exact tests. FINDINGS: A total of 392 randomized clinical trials were included. In comparison with the period from 2010-2015, the reporting rate for race and ethnicity in US studies has increased from 59.8% to 71.9% (P = .05). However, the proportion of reporting articles including at least 20% non-White representation remains unchanged at 38.1% with 37 of 97 reporting randomized clinical trials in 2010-2015 and 53 of 139 reporting randomized clinical trials in 2015-2020 (P = .99). Psoriasis studies included the least diversity, with 12.1% of studies recording at least 20% non-White participants and 29.5% of studies recording at least 45% female participants. CONCLUSIONS AND RELEVANCE: The findings of this systematic review suggest that reporting racial and ethnic data since 2010-2015 has become more transparent. However, inclusion of representative patient populations may still be considered inadequate, particularly in psoriasis studies. Diversity in clinical trials is important for representation of the affected patient populations, and additional efforts are warranted in support of this endeavor.


Asunto(s)
Dermatitis Atópica , Dermatología , Psoriasis , Etnicidad , Femenino , Humanos , Masculino , Proyectos de Investigación
14.
Dermatol Clin ; 39(3): 407-415, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34053594

RESUMEN

Alopecia areata (AA) is a chronic, relapsing, autoimmune disorder characterized by patchy nonscaring hair loss. Although the pathogenesis of alopecia areata is not yet completely elucidated, loss of immune privilege in anagen stage hair follicles is widely accepted to play a key role. Several cytokines that depend on Janus kinase signaling have been identified to be involved in AA, including interleukin (IL)-2, IL-7, IL-15, IL-21, and interferon-γ, making Janus kinase inhibitors an attractive therapeutic target. Available information indicates that about 70% of patients with AA experience significant regrowth, but interruption of treatment is associated with disease recurrence.


Asunto(s)
Alopecia Areata , Enfermedades Autoinmunes , Inhibidores de las Cinasas Janus , Alopecia Areata/tratamiento farmacológico , Folículo Piloso , Humanos , Interleucina-2 , Inhibidores de las Cinasas Janus/uso terapéutico
15.
BMC Res Notes ; 14(1): 165, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33933148

RESUMEN

OBJECTIVE: In the U.S., health insurance is a crucial determinant of the affordability of healthcare services and access to care. Population-based studies indicate Americans do not have an adequate understanding of their insurance plans and face difficulties navigating their health insurance coverage. The purpose of this pilot study is to collect qualitative data using a key informant interview format to learn about the acceptability, feasibility and implementation of a newly devised online health insurance navigation tool (HINT). RESULTS: A total of 57 Florida residents completed the 18-item HINT web-based survey tool and provided feedback on their experience, of which 63.2% were women, 40.7% Black race, and had average sample age of 46.9 years. Participants reported the web tool to be of good length, easy readability, relevant, and overall helpful for insurance selection. All respondents reported that they would use the tool themselves should they find themselves in the process of selecting an insurance plan and 98.2% of respondents reported that they would suggest the web tool to a family or friend. The average time it took to complete the questionnaire was 4 min and 20 s.The HINT tool met study criteria on feasibility, implementation, and acceptability among study participants.


Asunto(s)
Seguro de Salud , Internet , Estudios de Factibilidad , Femenino , Florida , Humanos , Cobertura del Seguro , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estados Unidos
16.
Clin Dermatol ; 38(5): 541-546, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33280801

RESUMEN

National experience demonstrates that most physicians will undergo a job change within the first few years of practice. Due to shifting payment models, personal preferences, and financial burden, among other factors, job transitions between private practice and academic medicine are expected. With the rising shortage of dermatologists and an increase in demand for dermatologic services, this particular topic is salient due to the impact on patient care, graduate medical education, and advances in research and medicine. The balance between these elements is fundamental for the future of dermatologic education and care. We address the challenges faced by dermatologists in both the academic and private practice settings, while offering insight into the motivations and barriers in the transition between the two.


Asunto(s)
Movilidad Laboral , Dermatólogos , Práctica Privada , Dermatólogos/provisión & distribución , Dermatología/educación , Educación de Postgrado en Medicina/tendencias , Humanos , Motivación
18.
Oncol Rep ; 34(3): 1487-93, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26134602

RESUMEN

Heterologous expression of the Drosophila melanogaster multi-substrate deoxyribonucleoside kinase (Dm-dNK) increases the sensitivity of cancer cells to several cytotoxic nucleoside analogs. Thus, it may be used as a suicide gene in combined gene/chemotherapy treatment of cancer. To further characterize this potential suicide gene, we constructed two retroviral vectors that enabled the expression of Dm-dNK in cancer cells. One vector harbored the wild­type enzyme that localized to the nucleus. The other vector harbored a mitochondrial localized mutant enzyme that was constructed by deleting the nuclear localization signal and fusing it to a mitochondrial import signal of cytochrome c oxidase. A thymidine kinase-deficient osteosarcoma cell line was transduced with the recombinant viruses. The sensitivity and bystander cell killing in the presence of pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)­2'­deoxyuridine and 1-ß-D-arabinofuranosylthymine were investigated. Tanshinone IIA is a constituent of Danshen; a traditional Chinese medicine used in the treatment of cardiovascular diseases. This study also looked at the influence of Tanshinone IIA on the bystander effect and the underlying mechanisms. We showed that sensitivity of the osteosarcoma cell line to the nucleoside analogs and the efficiency of bystander cell killing were independent of the subcellular localization of Dm-dNK. The enhanced effect of tanshinone IIA on the bystander effect was related to the increased expression of Cx43 and Cx26.


Asunto(s)
Abietanos/administración & dosificación , Terapia Genética , Osteosarcoma/tratamiento farmacológico , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Animales , Efecto Espectador , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Conexina 26 , Conexinas , Desoxiuridina/administración & dosificación , Desoxiuridina/análogos & derivados , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Galactosa/administración & dosificación , Galactosa/análogos & derivados , Vectores Genéticos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Señales de Localización Nuclear/genética , Osteosarcoma/genética , Osteosarcoma/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/biosíntesis , Retroviridae/genética , Timina/administración & dosificación , Timina/análogos & derivados
19.
Oncol Lett ; 8(6): 2642-2648, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25364442

RESUMEN

The mammalian target of rapamycin (mTOR)/eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) pathway plays a critical role in cell growth, survival and angiogenesis, and has been demonstrated to correlate with human epidermal growth factor receptor 2 (HER2) status. Neoadjuvant chemotherapy (NAC), also known as preoperative therapy, is now well established in the treatment of inoperable locally advanced and inflammatory breast cancer. In vitro study has shown that mTOR inhibitors, together with cytotoxic agents, exhibit tumor cell killing activity. A number of non-randomized studies in HER2-positive trastuzumab-resistant metastatic breast cancer have revealed the antitumor activity of mTOR inhibitors when used together with standard chemotherapy plus trastuzumab. In the present study, the expression levels of phosphorylated (p)-mTOR and p-4E-BP1 were analyzed in breast cancer patients prior to and following NAC, to determine whether p-mTOR and p-4E-BP1 affect the response to NAC and the subsequent survival. Formalin-fixed, paraffin-embedded tissues representing matched pairs of core biopsy (pre-NAC) and surgical specimen (post-NAC) from 83 patients with invasive ductal carcinomas were collected. Immunohistochemistry was performed to evaluate the expression of p-mTOR and p-4E-BP1 using a semi-quantitative scoring system by two pathologists. It was found that the expression of p-mTOR and p-4E-BP1 was downregulated following NAC. The decrease in mTOR expression following NAC was found to positively correlate with HER2 expression and the reduction of tumor sizes. The high expression of p-mTOR and p-4E-BP1 in pre-NAC specimens was associated with poor disease-free survival (DFS). Furthermore, the high expression of p-mTOR in post-NAC specimens was associated with poor DFS, regardless of whether the expression was high or low in the pre-NAC specimens. In conclusion, NAC was found to decrease the expression levels of p-mTOR and p-4E-BP1. The p-mTOR expression post-NAC may potentially serve as a predictor for DFS. However, further study is required to clarify the mechanism and to evaluate the predictive value of the phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway in NAC.

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