Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients.
The purpose of this article is to review the imaging features of thoracic epithelioid hemangioendotheliomas with pathologic correlation. The thoracic manifestation of epithelioid hemangioendotheliomas is one of three different CT patterns: multiple pulmonary nodules, multiple pulmonary reticulonodular opacities, or diffuse infiltrative pleural thickening. Without any evidence of histological malignancy, malignant features (multiplicity of pulmonary nodules, hepatic or bone involvement, lymphangitic tumor spread, and infiltrative pleural masses) are characteristic of these infrequent tumors.
The tumor microenvironment influences tumor progression, invasion, and metastasis. This study determined the expression levels of epithelial-mesenchymal transition (EMT) factors according to zone and their correlation with mammographic breast density and investigated the prognostic value of EMT factors.The clinical and pathological data of invasive carcinoma and ductal carcinoma in situ were reviewed. Primary breast tissue samples were evaluated using immunohistochemistry (IHC) staining of the EMT-associated markers, including α-SMA, vimentin, MMP-9, and CD34. The expression levels were analyzed in three areas: the tumor center, interface, and distal zones. EMT factors were correlated with mammographic breast density and oncologic outcomes.An overall EMT phenotype conversion from positive to negative was seen in 55.7% of α-SMA- and 34.4% of MMP-9-positive cells between the tumor center and interface zones, which was significantly different (p<0.05). Most changes in EMT expression from the center to the distal zone were from positive to negative, but 23.0% of CD34-expressing cells showed negative to positive conversion. The proportion of α-SMA, vimentin, and MMP-9 expression was higher in the non-dense breast group compared to the dense breast group in the interface and distal zones (p<0.05). CD34 expression in the distal zone was an independent favorable prognostic factor for disease-free survival (p=0.039).The differential expression of EMT markers in each zone suggests heterogeneous cancer cell populations within each zone of breast cancer. EMT factor expression can also interplay between breast density stroma and geographical tumor zone.
Purpose: To identify predictive factors of upstaging from diagnosed ductal carcinoma in situ (DCIS) to invasive cancer after surgical excision. Methods: One hundred seventy-four patients diagnosed with DCIS based on biopsies between January 2009 and December 2014 were evaluated. Patientsâ clinicopathological variables were assessed to identify predictive factors of invasive carcinoma from final pathology. Results: One hundred seventy-four cases of DCIS were included. Of these, 42 were upstaged to invasive carcinoma on the final excision. Preoperative features such as age 40 years or younger at diagnosis, presence of a palpable mass, ultrasonography (USG)-guided core needle biopsy, tumor size â¥20 mm on USG, high grade DCIS, cribriform DCIS, comedo necrosis, presence of intraluminal calcification, estrogen receptor negativity, progesterone receptor negativity and triple-negative subtype were significantly associated with the risk of invasive carcinoma. Multivariate analysis showed that a tumor size â¥20 mm on USG and triple negative subtype were independently associated with upstaging. Conclusion: Tumor size â¥20 mm on USG and triple-negative subtype were independently associated with the upstaging of DCIS to invasive cancer. Keywords: Breast neoplasms; Noninfiltrating intraductal carcinoma>
Background: Cancer cachexia is a complex metabolic syndrome that severely impacts mobility, treatment strategies, and life quality of the patients. However, no treatments are available to mitigate the debilitating consequences of cancer cachexia. Ghrelin is a hormone released from the stomach that increases appetite upon acylation by binding to GHSR1a receptors in the brain. Because of its orexigenic effects and increases in body weight, ghrelin GHSR1a receptor analogs were tested as clinical trials to mitigate muscle wasting and loss of strength in cancer patients in several countries. The analogs (i.e., Anamorelin) increased body weight of the non-small lung cancer patients in European countries and Japan, but failed to increase strength, which is the critical component in cancer cachexia. Mainly due to the lack of improvement in strength and patients’ quality of life, Anamorelin was not approved for clinical use in Europe. While the lack of increases in strength is, at least in part, associated with the adipogenic effects of acylated ghrelin, unacylated ghrelin directly improves satellite cell renewal, muscle growth, and mitochondrial function independent of GHSR1a receptor activation and increases in appetite. Unacylated ghrelin is the predominant population in circulation comprising proximately 90-95% of total ghrelin in humans and rodents. Hypothesis: Unacylated ghrelin projects against muscle wasting, loss of strength, and metabolic dysfunction of tumor bearing mice. Methods and Results: Supplementing the cancer cell conditioned medium (CM) with unacylated ghrelin preserved myotube size. Unacylated ghrelin also diminished the cancer cell CM-induced upregulation of MuRF-1, muscle specific ubiquitin ligase. Interestingly, unacylated ghrelin normalized transcriptional upregulation of denervation markers (i.e., sarcolipin, Runx1, GADD45a) in myotubes treated with CM. To further investigate the therapeutic effects of unacylated ghrelin in vivo, we inoculated lung cancer cell line (LL2, ATCC®) in the flank of 4 months old male mice. Two weeks after the injection prior to development of cachexia, mice were provided with unacylated ghrelin containing drinking water or untreated water as control. Tumor bearing (TB) mice treated with unacylated ghrelin showed 30-40% increases in gastrocnemius and quadriceps weights, while soleus muscle mass was unchanged. In addition to the muscle quantity, unacylated ghrelin increased force generating capacity was also improved by unacylated ghrelin. Notably, unacylated ghrelin increased mitochondrial oxygen consumption rate and protected against neuromuscular junction disruption and denervation in TB control mice. Conclusion: Unacylated ghrelin protects against cancer cachexia by targeting multiple risk factors in skeletal muscle wasting, including protein balance, metabolic alterations, and neuromuscular junction disruption. Our findings show protective effects of unacylated ghrelin against cachexia and neuromuscular impairment in tumor bearing mice, indicating its therapeutic potential in cancer patients. NIA R00 064143 to Ahn B. Pilot funds from the Center for Redox Biology in Medicine, and Cancer Genetics and Metabolism program at the Wake Forest Baptist Comprehensive Cancer Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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