Triple Negative Breast Cancer (TNBC) immunotherapy has recently shown promising approach. However, some TNBC patients presented with resistance. One of the reasons was attributed to the excessive ...release of cytokines at the tumor microenvironment (TME) such as Tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Fine regulation of these cytokines’ levels via non-coding RNAs (ncRNAs) might alleviate the immune quiescent nature of TME at TNBC tumors. However, the extrapolation of ncRNAs as therapeutic tools is highly challenging. Therefore, disentanglement the nature for the isolation of natural compounds that could modulate the ncRNAs and their respective targets is an applicable translational therapeutic approach. Hence, this study aimed to targeting the chief immune suppressive cytokines at the TME (TNF-α and IL-10) via ncRNAs and to examine the effects of Rosemary aerial parts extract on the expression levels of these ncRNAs in TNBC. Results revealed miR-17-5p as a dual regulator of TNF-α and IL-10. Moreover, an intricate interaction has been shown between miR-17-5p and the oncogenic lncRNAs: MALAT1 and H19. Knocking down of MALAT1 and/or H19 caused an induction in miR-17-5p and reduction in TNF-α and IL-10 expression levels. miR-17-5p was found to be down-regulated, while TNF-α, IL-10, MALAT1 and H19 were up-regulated in BC patients. Forced expression of miR-17-5p in MDA-MB-231 cells reduced TNF-α, IL-10, MALAT1 and H19 expression levels, as well as several BC hallmarks. In a translational approach, ursolic acid (UA) isolated from rosemary induced the expression of miR-17-5p, MALAT1 and decreased H19 expression levels. In conclusion, this study suggests miR-17-5p as a tumor suppressor and an immune-activator miRNA in BC through tuning up the immunological targets TNF-α, IL-10 at the TME and the oncological mediators MALAT1 and H19 lncRNAs.
This study aimed to identify the tumor mutation burden (TMB) value in Egyptian breast cancer (BC) patients. Moreover, to find the best TMB prediction model based on the expression of estrogen (ER), ...progesterone (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation index Ki-67.
The Ion AmpliSeq Comprehensive Cancer Panel was used to determine TMB value of 58 Egyptian BC tumor tissues. Different machine learning models were used to select the optimal classification model for prediction of TMB level according to patient's receptor status.
The measured TMB value was between 0 and 8.12/Mb. Positive expression of ER and PR was significantly associated with TMB ≤ 1.25 (OR =0.35, 95% CI: 0.04-2.98), (OR = 0.17, 95% CI= 0.02-0.44) respectively. Ki-67 expression positive was significantly associated with TMB >1.25 than those who were Ki-67 expression negative (OR = 9.33, 95% CI= 2.07-42.18). However, no significant differences were observed between HER2 positive and HER2 negative groups. The optimized logistic regression model was TMB = -27.5 -1.82 ER - 0.73 PR + 0.826 HER2 + 2.08 Ki-67.
Our findings revealed that TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67.
Breast cancer (BC) is the most diagnosed cancer and the leading cause of global cancer incidence in 2020. It is quite known that highly invasive cancers have disrupted metabolism that leads to the ...creation of an acidic tumor microenvironment. Among the proton-sensing G protein-coupled receptors is GPR68. In this study, we aimed to explore the expression pattern of GPR68 in tissues from BC patients as well as different BC cell lines.
In-silico tools were used to assess the expression of GPR68 in BC patients. The expression pattern was validated in fresh and paraffin-embedded sections of BC patients using qPCR and immunohistochemistry (IHC), respectively. Also, in-silico tools investigated GPR68 expression in different BC cell lines. Validation of GPR68 expression was performed using qPCR and immunofluorescence techniques in four different BC cell lines (MCF-7, MDA-MB-231, BT-549 and SkBr3).
GPR68 expression was found to be significantly increased in BC patients using the in-silico tools and validation using qPCR and IHC. Upon classification according to the molecular subtypes, the luminal subtype showed the highest GPR68 expression followed by triple-negative and Her2-enriched cells. However, upon validation in the recruited cohort, the triple-negative molecular subtype of BC patients showed the highest GPR68 expression. Also, in-silico and validation data revealed that the triple-negative breast cancer cell line MDA-MB-231 showed the highest expression of GPR68.
Therefore, this study highlights the potential utilization of GPR68 as a possible diagnostic and/or prognostic marker in BC.
Background
Breast conserving surgery (BCS) has been a standard procedure for the treatment of breast cancer instead of mastectomy whenever possible. Lateral chest wall perforator flaps are one of the ...volume replacement techniques that participate in increasing the rate of BCS especially in small- to moderate-sized breasts with good cosmetic outcome. In this study, we tried to evaluate the outcome of those flaps as an oncoplastic procedure instead of the conventional flaps.
Methods
This study included 26 patients who underwent partial mastectomy with immediate reconstruction using lateral chest wall perforator flaps in the period from October 2019 to November 2020. The operative time, techniques, and complications were recorded. The cosmetic outcome was assessed 3 months post-radiation therapy through a questionnaire and photographic assessment.
Results
Lateral intercostal artery perforator (LICAP), lateral thoracic artery perforator (LTAP) and combined flaps were performed in 24, 1, and 1 patients, respectively. The mean operative time was 129.6 ± 13.2 min. The flap length ranged from 10 to 20 cm and its width from 5 to 9 cm. Overall patients’ satisfaction was observed to be 88.5% as either excellent or good and the photographic assessment was 96.2% as either excellent or good.
Conclusions
Lateral chest wall perforator flaps are reliable and safe option for partial breast reconstruction with an acceptable aesthetic outcome. In the era of oncoplastic breast surgery, they deserve to gain attention especially with the advantages of some modifications added to the classic technique.
Abstract Background Hydrogen sulfide (H 2 S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). ...Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H 2 S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H 2 S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H 2 S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H 2 S generation. Thus, the aim of this work is to escape the H 2 S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. Methods BC female patients ( n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H 2 S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. Results miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H 2 S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. Conclusion This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H 2 S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.
Background
Management of the node-positive axilla after neoadjuvant chemotherapy is controversial. The aim of this study is to predict the group of patients who may require a less invasive approach ...for axillary management. One possible group are patients with pathological complete response of the primary after chemotherapy.
Results
A unicentral retrospective cohort study including all breast cancer patients with axillary node metastases at presentation who received neoadjuvant chemotherapy resulting in pathological complete response. Pathological complete response in the axillary lymph nodes was recorded. A correlation between the response in the primary tumour and the lymph nodes was assessed. A subgroup analysis was conducted for different biological groups.
Complete response was seen in the axillary nodes in 80.5% of patients. Patients with lobular cancer were less likely to show a similar response in the axilla as the primary tumour (
p
= 0.077). A higher incidence of axillary response was observed in HER2-positive tumours (
p
= 0.082). All patients with grade 3 tumours achieved complete response in the axilla (
p
= 0.094). Patients with negative or weak positive hormone receptor status had a significantly higher rate of complete response in the axilla compared to strongly positive hormone receptor status (OR, 7.8; 95% CI, 1.7–34.5;
p
= 0.007).
Conclusion
A less invasive axillary surgery may be safely recommended in selected group of node-positive patients after neoadjuvant chemotherapy when the primary tumour shows complete response. This group may include HER2-positive, ER-negative and grade 3 tumours. Less response is expected in ER-positive and lobular carcinoma even with complete response in the primary.
To demonstrate the feasibility and accessibility of performing adequate mastectomy to extirpate the breast tissue, along with en-block formal axillary dissection performed from within the same ...incision. We also compared different methods of immediate breast reconstruction used to fill the skin envelope to achieve the best aesthetic results.
38 patients with breast cancer underwent skin-sparing mastectomy with formal axillary clearance, through a circum-areolar incision. Immediate breast reconstruction was performed using different techniques to fill in the skin envelope. Two reconstruction groups were assigned; group 1: Autologus tissue transfer only (n=24), and group 2: implant augmentation (n=14).
The techniques used included filling in the skin envelope using Extended Latissimus Dorsi flap (18 patients) and Pedicled TRAM flap (6 patients).
Subpectoral implants(4 patients), a rounded implant placed under the pectoralis major muscle to augment an LD reconstructed breast. LD pocket (10 patients), an anatomical implant placed over the pectoralis major muscle within a pocket created by the LD flap. No contra-lateral procedure was performed in any of the cases to achieve symmetry.
All cases underwent adequate excision of the breast tissue along with en-block complete axillary clearance (when indicated), without the need for an additional axillary incision.
Eighteen patients underwent reconstruction using extended LD flaps only, six had TRAM flaps, four had augmentation using implants placed below the pectoralis muscle along with LD flaps, and ten had implants placed within the LD pocket.
Breast shape, volume and contour were successfully restored in all patients.
Adequate degree of ptosis was achieved, to ensure maximal symmetry.
Skin Sparing mastectomy through a circum-areolar incision has proven to be a safe and feasible option for the management of breast cancer in Egyptian women, offering them adequate oncologic control and optimum cosmetic outcome through preservation of the skin envelope of the breast when ever indicated. Our patients can benefit from safe surgery and have good cosmetic outcomeby applying different reconstructive techniques.
Hydrogen sulfide (H
S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), ...cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H
S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H
S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H
S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H
S generation. Thus, the aim of this work is to escape the H
S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells.
BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H
S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays.
miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H
S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins.
This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H
S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.
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