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Gland Surgery May 2024Perforator flaps have revolutionized autologous breast reconstruction, introducing both free and pedicled options as well as the potential for combining flaps. These... (Review)
Review
BACKGROUND AND OBJECTIVE
Perforator flaps have revolutionized autologous breast reconstruction, introducing both free and pedicled options as well as the potential for combining flaps. These versatile techniques can be utilized in massive weight loss (MWL) patients, effectively addressing both functional and aesthetic challenges by using their excess skin. This review aims to explore literature on combined pedicled and free perforator flaps for total breast reconstruction, and share our own experience in the field.
METHODS
A PubMed search up to June 2023 employed Medical Subject Headings (MeSH) terms such as (("combined") OR ("stacked") OR ("conjoined") AND ("perforator flaps")) AND ("breast reconstruction"). Publications in English and Scandinavian languages were manually screened for relevance, and supplemental sources were also reviewed.
KEY CONTENT AND FINDINGS
Limited studies exist on using combined pedicled and free flaps for total breast reconstruction, although combined free flaps are more common. Perforators around the breast base, offer multiple flap options for single or combined use. In our series of 10 women, four underwent total breast reconstruction with a combination of flip-over internal mammary artery perforator (IMAP) flap and thoracodorsal artery perforator (TDAP) flap. Another subset of four, who were MWL patients, received combined TDAP and superior epigastric artery perforator (SEAP) flaps, along with body contouring procedures such as upper body lifts and vertical abdominoplasties, addressing excess skin and improving silhouette. One remaining MWL patient had deflated breasts restored using TDAP and SEAP flaps, along with an upper and lower body lift and vertical abdominoplasty. The last MWL patient underwent a risk-reducing mastectomy, also reconstructed with TDAP and SEAP flaps, and received an upper body lift and vertical abdominoplasty.
CONCLUSIONS
Combined perforator flap techniques for combined body contouring and breast reconstruction seems safe and especially suitable for MWL patients. They offer a surgical alternative merging body contouring and breast reconstruction in cases where free flap procedures seem less favorable due to skin laxity and deflation of donor sites. However, limited literature on the topic calls for further studies.
PubMed: 38845826
DOI: 10.21037/gs-23-397 -
PloS One 2024During lactation, the murine mammary gland is responsible for a significant increase in circulating serotonin. However, the role of mammary-derived serotonin in energy...
During lactation, the murine mammary gland is responsible for a significant increase in circulating serotonin. However, the role of mammary-derived serotonin in energy homeostasis during lactation is unclear. To investigate this, we utilized C57/BL6J mice with a lactation and mammary-specific deletion of the gene coding for the rate-limiting enzyme in serotonin synthesis (TPH1, Wap-Cre x TPH1FL/FL) to understand the metabolic contributions of mammary-derived serotonin during lactation. Circulating serotonin was reduced by approximately 50% throughout lactation in Wap-Cre x TPH1FL/FL mice compared to wild-type mice (TPH1FL/FL), with mammary gland and liver serotonin content reduced on L21. The Wap-Cre x TPH1FL/FL mice had less serotonin and insulin immunostaining in the pancreatic islets on L21, resulting in reduced circulating insulin but no changes in glucose. The mammary glands of Wap-Cre x TPH1FL/FL mice had larger mammary alveolar areas, with fewer and smaller intra-lobular adipocytes, and increased expression of milk protein genes (e.g., WAP, CSN2, LALBA) compared to TPH1FL/FL mice. No changes in feed intake, body composition, or estimated milk yield were observed between groups. Taken together, mammary-derived serotonin appears to contribute to the pancreas-mammary cross-talk during lactation with potential implications in the regulation of insulin homeostasis.
Topics: Animals; Lactation; Serotonin; Female; Mammary Glands, Animal; Mice; Liver; Tryptophan Hydroxylase; Mice, Inbred C57BL; Pancreas; Insulin
PubMed: 38837989
DOI: 10.1371/journal.pone.0304910 -
Breast Cancer Research : BCR Jun 2024The aberrant amplification of mammary luminal progenitors is at the origin of basal-like breast cancers associated with BRCA1 mutations. Integrins mediate cell-matrix...
BACKGROUND
The aberrant amplification of mammary luminal progenitors is at the origin of basal-like breast cancers associated with BRCA1 mutations. Integrins mediate cell-matrix adhesion and transmit mechanical and chemical signals that drive epithelial stem cell functions and regulate tumor progression, metastatic reactivation, and resistance to targeted therapies. Consistently, we have recently shown that laminin-binding integrins are essential for the expansion and differentiation of mammary luminal progenitors in physiological conditions. As over-expression of the laminin-binding α6 integrin (Itgα6) is associated with poor prognosis and reduced survival in breast cancer, we here investigate the role of Itgα6 in mammary tumorigenesis.
METHODS
We used Blg-Cre; Brca1; Trp53 mice, a model that phenocopies human basal-like breast cancer with BRCA1 mutations. We generated mutant mice proficient or deficient in Itgα6 expression and followed tumor formation. Mammary tumors and pretumoral tissues were characterized by immunohistochemistry, flow cytometry, RT-qPCR, Western blotting and organoid cultures. Clonogenicity of luminal progenitors from preneoplastic glands was studied in 3D Matrigel cultures.
RESULTS
We show that Itga6 deletion favors activation of p16 cell cycle inhibitor in the preneoplastic tissue. Subsequently, the amplification of luminal progenitors, the cell of origin of Brca1-deficient tumors, is restrained in Itgα6-deficient gland. In addition, the partial EMT program operating in Brca1/p53-deficient epithelium is attenuated in the absence of Itgα6. As a consequence of these events, mammary tumor formation is delayed in Itgα6-deficient mice. After tumor formation, the lack of Itgα6 does not affect tumor growth but rather alters their differentiation, resulting in reduced expression of basal cell markers.
CONCLUSIONS
Our data indicate that Itgα6 has a pro-tumorigenic role in Blg-Cre; Brca1; Trp53 mice developing basal-like mammary tumors. In particular, we reveal that Itgα6 is required for the luminal progenitor expansion and the aberrant partial EMT program that precedes the formation of BRCA1 deficient tumors.
Topics: Animals; Integrin alpha6; Female; Tumor Suppressor Protein p53; Mice; BRCA1 Protein; Breast Neoplasms; Humans; Neoplastic Stem Cells; Cell Proliferation; Stem Cells; Gene Deletion; Cell Transformation, Neoplastic
PubMed: 38835038
DOI: 10.1186/s13058-024-01851-4 -
Journal of Dairy Science May 2024This study aimed to evaluate the impact of heat stress on mammary epithelial cell (MEC) losses into milk, secretory mammary tissue structure, and mammary epithelial cell...
This study aimed to evaluate the impact of heat stress on mammary epithelial cell (MEC) losses into milk, secretory mammary tissue structure, and mammary epithelial cell activity. Sixteen multiparous Holstein cows (632 ± 12 kg BW) approximately 100 d in milk housed in climate-controlled rooms were paired by body weight and randomly allocated to one of 2 treatments, heat stress (HS) or pair feeding thermoneutral (PFTN) using 2 cohorts. Each cohort was subjected to 2 periods of 4 d each. In period 1, both treatments had ad libitum access to a common total mixed ration and were exposed to a controlled daily temperature-humidity index (THI) of 64. In period 2, HS cows were exposed to controlled cyclical heat stress (THI: 74 to 80), while PFTN cows remained at 64 THI and daily dry matter intake was matched to HS. Cows were milked twice daily, and milk yield was recorded at each milking. Individual milk samples on the last day of each period were used to quantify MEC losses by flow cytometry using butyrophilin as a cell surface marker. On the final day of period 2, individual bovine mammary tissue samples were obtained for histomorphology analysis, assessment of protein abundance, and evaluation of gene expression of targets associated with cellular capacity for milk and milk component synthesis, heat response, cellular proliferation, and autophagy. Statistical analysis was performed using the GLIMMIX procedure of SAS. Milk yield was reduced by 4.3 kg by HS (n = 7) compared with PFTN (n = 8). Independent of treatment, MEC in milk averaged 174 cells/mL (2.9% of total cells). There was no difference between HS vs. PFTN cows for MEC shed or concentration in milk. Alveolar area was reduced 25% by HS, and HS had 4.1 more alveoli than PFTN. Total number of nucleated MEC per area were greater in HS (389 ± 1.05) compared with PFTN (321 ± 1.05); however, cell number per alveolus was similar between groups (25 ± 1.5 vs. 26 ± 1.4). There were no differences in relative fold expression for GLUT1, GLUT8, CSN2, CSN3, LALBA, FASN, HSPA5, and HSPA8 in HS compared with PFTN. Immunoblotting analyses showed a decrease abundance for phosphorylated STAT5 and S6K1, and an increase in LC3 II in HS compared with PFTN. These results suggest that even if milk yield differences and histological changes occur in the bovine mammary gland after 4 d of heat exposure, MEC loss into milk, nucleated MEC number per alveolus, and gene expression of nutrient transport, milk component synthesis, and heat stress related targets are unaffected. In contrast, the abundance of proteins related to protein synthesis and cell survival decreased significantly, while an upregulation of proteins associated with autophagy in HS compared with PFTN.
PubMed: 38825136
DOI: 10.3168/jds.2024-24809 -
Tropical Animal Health and Production May 2024The aim of the present study was to examine the mammary gland of dromedary camels using ultrasonography, endoscopy and radiography. These techniques are easy to perform...
The aim of the present study was to examine the mammary gland of dromedary camels using ultrasonography, endoscopy and radiography. These techniques are easy to perform in the field and feasible to diagnose pathological conditions of the mammary gland. Udders of 49 slaughtered and 26 adult dromedary camels submitted for necropsy were used for the examinations. Additionally, 11 lactating female dromedary camels were selected for the ultrasonographic udder examination. The transition from the milk ducts into the udder cistern, the teat cistern and the teat canals were examined in individual udders. Teat cistern length, teat end width, teat wall thickness, teat cistern width and middle cistern wall thickness were measured using ultrasonography. The measurements resulted in mean values of the teat cistern length of 37.3 mm, the teat end width of 2.0 mm, the teat wall thickness of 4.4 mm, the teat cistern width of 8.2 mm and the cistern wall thickness of 3.5 mm. The teat wall was differentiated into three layers, a hyperechoic outer layer, a hypoechoic middle layer and a hyperechoic inner layer. The mid cistern wall was hyperechoic. Endoscopic examination is an easy to perform and practicable method for examining the inner structures of the teats of dead animals; however, the feasibility has not been shown in lactating animals yet. Ring-like folds were present in the teat cistern, which protruded horizontally into the lumen. It was also possible to visualize the branchlike transition of the teat cistern into the larger milk ducts. Radiographic examination using barium sulfate contrast medium showed that the teat cistern ends in a network of initially wide but branching and narrowing milk ducts. The two teat canals and cisterns are completely independent of each other and there is no communication between the glandular tissue of the two canals and cisterns.
Topics: Animals; Camelus; Female; Mammary Glands, Animal; Endoscopy; Radiography; Ultrasonography
PubMed: 38819754
DOI: 10.1007/s11250-024-04009-8 -
Maternal behaviours disrupted by Gprasp2 deletion modulate neurodevelopmental trajectory in progeny.Scientific Reports May 2024Autism spectrum disorders (ASDs) are known to present sex-specific differences. At the same time, understanding how maternal behaviours are affected by pathogenic...
Autism spectrum disorders (ASDs) are known to present sex-specific differences. At the same time, understanding how maternal behaviours are affected by pathogenic mutations is crucial to translate research efforts since rearing may recursively modulate neurodevelopment phenotype of the progeny. In this work, we focused on the effects of Gprasp2 deletion in females and its impact in progeny care and development. Female mice, wild-type (WT), Gprasp2 (HET) or Gprasp2 (KO) mutants and their progeny were used and behavioural paradigms targeting anxiety, memory, maternal care, and other social behaviours were performed. Analysis of communication was carried out through daily recordings of ultrasonic vocalizations in isolated pups and cross-fostering experiments were performed to understand the effect of maternal genotype in pup development. We found that Gprasp2 females presented striking impairments in social and working memory. Females also showed disruptions in maternal care, as well as physiological and molecular alterations in the reproductive system and hypothalamus, such as the structure of the mammary gland and the expression levels of oxytocin receptor (OxtR) in nulliparous versus primiparous females. We observed alterations in pup communication, particularly a reduced number of calls in Gprasp2 KO pups, which resulted from an interaction effect of the dam and pup genotype. Cross-fostering mutant pups with wild-type dams rescued some of the early defects shown in vocalizations, however, this effect was not bidirectional, as rearing WT pups with Gprasp2 dams was not sufficient to induce significant phenotypical alterations. Our results suggest Gprasp2 mutations perturb social and working memory in a sex-independent manner, but impact female-specific behaviours towards progeny care, female physiology, and gene expression. These changes in mutant dams contribute to a disruption in early stages of progeny development. More generally, our results highlight the need to better understand GxE interactions in the context of ASDs, when female behaviour may present a contributing factor in postnatal neurodevelopmental trajectory.
Topics: Animals; Maternal Behavior; Female; Mice; Mice, Knockout; Social Behavior; Male; Receptors, G-Protein-Coupled; Behavior, Animal; Receptors, Oxytocin; Autism Spectrum Disorder; Vocalization, Animal; Gene Deletion
PubMed: 38816497
DOI: 10.1038/s41598-024-62088-x -
Current Developments in Nutrition Jun 2024Glutamine in milk is believed to play an important role in neonatal intestinal maturation and immune function. For lactating mothers, glutamine utilization is increased...
BACKGROUND
Glutamine in milk is believed to play an important role in neonatal intestinal maturation and immune function. For lactating mothers, glutamine utilization is increased to meet the demands of the enlarged intestine and milk production. However, the source of such glutamine during lactation has not been studied.
OBJECTIVES
We aimed to assess the effects of lactation on the expression of glutamine synthetase (GS) in the mammary gland and other tissues of lactating mice.
METHODS
Mouse tissues were sampled at 4 time points: 8-wk-old (virgin, control), post-delivery day 5 (PD5, early lactation), PD15 (peak lactation), and involution (4 days after weaning at PD21). We examined the gene expression and protein concentrations of GS and the first 2 enzymes of branched-chain amino acid catabolism: branched-chain aminotransferase 2 (BCAT2) and branched-chain ketoacid dehydrogenase subunit E1α (BCKDHA).
RESULTS
The messenger RNA (mRNA) expression and protein concentrations of GS in mammary glands were significantly lower at PD5 and PD15 compared with the control but were restored at involution. Within the mammary gland, GS protein was only detected in adipocytes with no evidence of presence in mammary epithelial cells. Compared with the control, mRNA and protein concentrations of BCAT2 and BCKDHA in mammary glands significantly decreased during lactation and involution. No changes in GS protein concentrations during lactation were found in the liver, skeletal muscle, and lung. In non-mammary adipose tissue, GS protein abundance was higher during lactation compared with the virgin.
CONCLUSIONS
This work shows that, within the mouse mammary gland, GS is only expressed in adipocytes and that the relative GS abundance in mammary gland sections is lower during lactation. This suggests that mammary adipocytes may be a site of glutamine synthesis in the lactating mouse. Identifying the sources of glutamine production during lactation is important for optimizing milk glutamine concentration to enhance neonatal and maternal health.
PubMed: 38813479
DOI: 10.1016/j.cdnut.2024.102168 -
Frontiers in Immunology 2024Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the...
Maternal immunization and vitamin A sufficiency impact sow primary adaptive immunity and passive protection to nursing piglets against porcine epidemic diarrhea virus infection.
Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the neonatal piglet immune system and given the high virulence of PEDV, improving passive lactogenic immunity is the best approach to protect suckling piglets against the lethal infection. We tested whether oral vitamin A (VA) supplementation and PEDV exposure of gestating and lactating VA-deficient (VAD) sows would enhance their primary immune responses and boost passive lactogenic protection against the PEDV challenge of their piglets. We demonstrated that PEDV inoculation of pregnant VAD sows in the third trimester provided higher levels of lactogenic protection of piglets as demonstrated by >87% survival rates of their litters compared with <10% in mock litters and that VA supplementation to VAD sows further improved the piglets' survival rates to >98%. We observed significantly elevated PEDV IgA and IgG antibody (Ab) titers and Ab-secreting cells (ASCs) in VA-sufficient (VAS)+PEDV and VAD+VA+PEDV sows, with the latter maintaining higher Ab titers in blood prior to parturition and in blood and milk throughout lactation. The litters of VAD+VA+PEDV sows also had the highest serum PEDV-neutralizing Ab titers at piglet post-challenge days (PCD) 0 and 7, coinciding with higher PEDV IgA ASCs and Ab titers in the blood and milk of their sows, suggesting an immunomodulatory role of VA in sows. Thus, sows that delivered sufficient lactogenic immunity to their piglets provided the highest passive protection against the PEDV challenge. Maternal immunization during pregnancy (± VA) and VA sufficiency enhanced the sow primary immune responses, expression of gut-mammary gland trafficking molecules, and passive protection of their offspring. Our findings are relevant to understanding the role of VA in the Ab responses to oral attenuated vaccines that are critical for successful maternal vaccination programs against enteric infections in infants and young animals.
Topics: Animals; Porcine epidemic diarrhea virus; Female; Swine; Pregnancy; Vitamin A; Coronavirus Infections; Antibodies, Viral; Swine Diseases; Immunity, Maternally-Acquired; Adaptive Immunity; Animals, Newborn; Lactation; Dietary Supplements; Vitamin A Deficiency; Immunization
PubMed: 38812505
DOI: 10.3389/fimmu.2024.1397118 -
Acta Cirurgica Brasileira 2024To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
PURPOSE
To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
METHODS
In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue.
RESULTS
IC50 value of temozolomide in MCF7 cell has been obtained as 103 μM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events.
CONCLUSIONS
The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.
Topics: Temozolomide; Animals; Apoptosis; Female; ErbB Receptors; Rats, Wistar; Antineoplastic Agents, Alkylating; Matrix Metalloproteinase 1; Cell Proliferation; Dacarbazine; Breast Neoplasms; Humans; MCF-7 Cells; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Reproducibility of Results; Rats; Mammary Neoplasms, Experimental
PubMed: 38808816
DOI: 10.1590/acb391624 -
BMC Veterinary Research May 2024Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer...
Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.
Topics: Animals; Dogs; Female; Mammary Neoplasms, Animal; Cell Line, Tumor; Proto-Oncogene Proteins c-akt; Dog Diseases; Phosphatidylinositol 3-Kinases; Cell Proliferation; Epithelial-Mesenchymal Transition; Signal Transduction; Phosphoinositide-3 Kinase Inhibitors
PubMed: 38807154
DOI: 10.1186/s12917-024-04085-w