•Epigenetic regulation of mitochondrial DNA (mtDNA) (mitoepigenetics) is an emerging and fast developing field of research.•Cancer cells contain oxidative stress-mediated defects in mtDNA repair ...system, nucleoid-based organization, and mitoepigenetic regulation.•Dysbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival.•Anti-cancer effects of several mitochondria-targeting agents warrant further testing in breast cancers.•Crosstalk mechanism between mitoepigenetics and cancer-associated mtDNA mutations is a promising therapy target in breast cancers.
Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.
Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in ...the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including “obesity,” “oncogenic signaling pathways,” “inflammation,” “surgery,” “radiotherapy,” “conventional therapies,” and “diet.” Multiple studies indicated that effective BC treatment requires the involvement of diet- and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients’ overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.
Background
This study reports the preliminary results of da Vinci robot XI robot‐assisted nipple‐sparing mastectomy immediate breast reconstruction (R‐NSMIBR) with gel implant and latissimus dorsi ...muscle flap.
Methods
A total of 15 patients who underwent R‐NSMIBR with gel implant and latissimus dorsi muscle flap surgery for breast cancer between September 2022 and November 2022 were evaluated.
Results
Mean total operative time for R‐NSMIBR was 361.9 ± 77.0 min. As the learning curve increased, the robot arm docking time decreased rapidly from the initial 25–10 min. Average total blood loss was 27.8 ± 10.7 mL and posterior surgical margin positivity rate was 0%. Perioperative complications and local recurrences or deaths were not observed at a mean follow‐up of 3 ± 1 month 15 patients were satisfied with postoperative aesthetic results.
Conclusions
R‐NSMIBR with a gel implant and latissimus dorsi muscle flap could be a new therapeutic option for breast reconstruction.
Several research reports delineated the significant role of miRNAs in cancer proliferation, and their modulatory role in cancer mitigation, and drug resistance. Melanoma cells have been acquiring ...stemness to several chemotherapeutic agents through drug efflux proteins, epigenetic modulation, and DNA repair. miRNAs could be applied as novel therapeutic modalities for treating several kinds of cancers to modulate these mechanisms involved in stemness. Nanocarriers to carry these tumor‐targeting miRNAs to modulate stemness are a prominent strategy to overcome their low penetrability, minimal stability, and nonspecificity. We have searched several public databases such as PubMed, Medline, Google scholar, and NLM and obtained the information pertinent to the miRNA‐based nanocarrier systems to target stemness through epigenetic modulation in melanomas. This review delineates that various miRNAs can modulate the stemness in melanomas by specific intricate epigenetic signaling, and other cell‐based signaling mechanisms. Specific nanocarrier formulations with specific miRNAs are optimal methods to deliver these miRNAs in order to achieve significant entrapment efficiency, loading efficiency, and stability. Furthermore, the combinatorial regimen of FDA‐approved chemotherapeutic molecules with tumor‐targeting miRNAs and chemotherapy combined with nanocarriers can efficiently deliver the utmost therapeutic window by targeting tumor matrix, invasion, metastasis, and angiogenesis in melanomas. Substantial research should focus on the clinical application of this gene therapy in melanomas using these low immunogenic, highly degradable, and biocompatible combinatorial nanotherapeutic regimens.
Background
da Vinci robot‐assisted axillary lymph node dissection (dVALND) can be a minimally invasive technique to minimize post‐operative complications.
Objective
To explore the clinical efficacy ...of dVALND in breast cancer (BC) patients for mitigating the postoperative complications than conventional ALND.
Methods
Total 60 female patients with BC were admitted to our hospitals since September 2018, and these patients segregated into two groups of 30 patients each. Modified radical mastectomy for BC was performed to the patients in both groups. In Group 1 (control group), ALND was performed using conventional mode of axillary lymph node surgery. In Group 2 (Test group), the dVALND was performed using da Vinci robot‐assisted surgery. Wound healing, aesthetic effect and patient's satisfaction were evaluated after conventional method and dVALND.
Results
Postoperative complications viz., wound infection (1/30 (3.33%), p < 0.05), fat necrosis (3/30 (10%), p < 0.05) and lymphedema of upper limbs (2/30 (6.67%), p < 0.05) were observed in dVALND than conventional surgery. Local recurrence or metastasis was minimized and overall aesthetic effect not observed during follow‐up.
Conclusion
dVALND improved the overall patient's quality of life by mitigating postoperative complications than ALND.
Upper limb lymphedema is one of the most common complications after breast cancer surgery and radiotherapy. At present, physical methods and surgical methods can be used for treatment. Surgical ...operations are mainly based on lymphovenous anastomosis and vascularized lymph node transfer. For these 2 surgical methods, we analyzed and compared the literature review and our own clinical experience. We summarized the differences between the 2 surgical techniques and the selection methods. We hope to help more young plastic surgeons and breast doctors understand how to treat upper limb lymphedema through surgical methods and help patients improve their quality of life.
Platinum derivatives are chemotherapeutic agents preferred for the treatment of cancers including breast cancer. Oxaliplatin is an anticancer drug that is in phase II studies to treat metastatic ...breast cancer. However, its usage is constrained by chemoresistance and dose-related side effects.
The objective of this study is to examine the combinatorial efficacy of brusatol, an Nrf2 blocker, with oxaliplatin (a proven FN3K blocker in our study) in mitigating breast cancer growth in vitro.
We performed cytotoxicity assays, combination index (CI) analysis, colony formation assays, apoptosis assays, and Western blotting.
Results of our study described the chemosensitizing efficacy of brusatol in combination with lowdose oxaliplatin against breast cancer through synergistic effects in both BT-474 and T47D cells. A significant mitigation in the migration rate of these cancer cells was observed with the combination regimen, which is equivalent to the IC-50 dose of oxaliplatin (125 μM). Furthermore, ROS-mediated and apoptotic modes of cell death were observed with a combinatorial regimen. Colony formation of breast cancer cell lines was mitigated with a combinatorial regimen of bursatol and oxaliplatin than the individual treatment regimen. FN3K expression downregulated with oxaliplatin in T47D cells. The mitigation of FN3K protein expression with a combination regimen was not observed but the Nrf2 downstream antioxidant signaling proteins were significantly downregulated with a combination regimen similar to individual drug regimens.
Our study concluded the combination efficacy of phytochemicals like brusatol in combination with low-dose oxaliplatin (FN3K blocker), which could enhance the chemosensitizing effect in breast cancer and minimize the overall dose requirement of oxaliplatin.
In recent times, robot-assisted surgery has been prominently gaining pace to minimize overall postsurgical complications with minimal traumatization, due to technical advancements in telerobotics and ...ergonomics. The aim of this review is to explore the efficiency of robot-assisted systems for executing breast surgeries, including microsurgeries, direct-to-implant breast reconstruction, deep inferior epigastric perforators-based surgery, latissimus dorsi breast reconstruction, and nipple-sparing mastectomy. Robot-assisted surgery systems are efficient due to 3D-based visualization, dexterity, and range of motion while executing breast surgery. The review describes the comparative efficiency of robot-assisted surgery in relation to conventional or open surgery, in terms of clinical outcomes, morbidity rates, and overall postsurgical complication rates. Potential cost-effective barriers and technical skills were also delineated as the major limitations associated with these systems in the clinical sector. Furthermore, instrument articulation of robot-assisted surgical systems (for example, da Vinci systems) can enable high accuracy and precision surgery due to its promising ability to mitigate tremors at the time of surgery, and shortened learning curve, making it more beneficial than other open surgery procedures.
Objective
To develop diagnostic radiomic model–based algorithm for pancreatic ductal adenocarcinoma (PDAC) grade prediction.
Methods
Ninety-one patients with histologically confirmed PDAC and ...preoperative CT were divided into subgroups based on tumor grade. Two histology-blinded radiologists independently segmented lesions for quantitative texture analysis in all contrast enhancement phases. The ratio of densities of PDAC and unchanged pancreatic tissue, and relative tumor enhancement (RTE) in arterial, portal venous, and delayed phases of the examination were calculated. Principal component analysis was used for multivariate predictor analysis. The selection of predictors in the binary logistic model was carried out in 2 stages: (1) using one-factor logistic models (selection criterion was
p
< 0.1); (2) using regularization (LASSO regression after standardization of variables). Predictors were included in proportional odds models without interactions.
Results
There were significant differences in 4, 16, and 8 texture features out of 62 for the arterial, portal venous, and delayed phases of the study, respectively (
p
< 0.1). After selection, the final diagnostic model included such radiomics features as DISCRETIZED HU standard, DISCRETIZED HUQ3, GLCM Correlation, GLZLM LZLGE for the portal venous phase of the contrast enhancement, and CONVENTIONAL_HUQ3 for the delayed phase of CT study. On its basis, a diagnostic model was built, showing AUC for grade ≥ 2 of 0.75 and AUC for grade 3 of 0.66.
Conclusion
Radiomics features vary in PDAC of different grades and increase the accuracy of CT in preoperative diagnosis. We have developed a diagnostic model, including texture features, which can be used to predict the grade of PDAC.
Key Points
•
A diagnostic algorithm based on CT texture features for preoperative PDAC grade prediction was developed.
•
The assumption that the scanning protocol can influence the results of texture analysis was confirmed and assessed.
•
Our results show that tumor differentiation grade can be assessed with sufficient diagnostic accuracy using CT texture analysis presented in this study.
Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications.
To this date, no single treatment method provides ...pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL).
To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy.
Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them.
As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.
