Cancer Clinic Research Articles

Nanomaterials Based on Functional Polymers for Sensitizing Cancer Radiotherapy.

Despite being the mainstay treatment for many types of cancer in clinic, radiotherapy is undertaking great challenges in overcoming a series of limitations. Radiosensitizers are promising agents capable of depositing irradiation energy and generating free radicals to enhance the radiosensitivity of tumor cells. Combining radiosensitizers with functional polymer-based nanomaterials holds great potential to improve biodistribution, circulation time, and stability in vivo. The derived polymeric nano-radiosensitizers can significantly improve the efficiency of tumor targeting and radiotherapy, and reduce the side effect to healthy tissues. In this review, an overview of functional polymer-based nanomaterials for radiosensitization in recent years is provided. Particular emphases are given to the action mechanisms, drug loading methods, targeting efficiencies, the impact on therapeutic effects, and biocompatibility of various radiosensitizing polymers, which are classified as polymeric micelles, dendrimers, polymeric nanospheres, nanoscale coordination polymers, polymersomes, and nanogels. The challenges and outlooks of polymeric nano-radiosensitizers are also discussed.

Manganese Dioxide-Based Nanocarrier Delivers Paclitaxel to Enhance Chemotherapy against Orthotopic Glioma through Hypoxia Relief.

Chemotherapy plays an important role in treating cancers in clinic. Hypoxia-mediated chemoresistance remains a major hurdle for effective tumor chemotherapy. Herein, a new class of tLyP-1-modified dopamine (DOPA)-β-cyclodextrin (CD)-coated paclitaxel (PTX)- and manganese dioxide (MnO2 )-loaded nanoparticles (tLyP-1-CD-DOPA-MnO2 @PTX) is developed to enhance glioma chemotherapy. The nanomedicine delivered to the tumor site decomposes in response to the weak acidity and high hydrogen peroxide in the tumor microenvironment (TME), resulting in collapse of the system to release PTX and generates Mn2+ and O2 . In a rat model of intracranial glioma, tLyP-1-CD-DOPA-MnO2 @PTX can efficiently pass through the blood-brain-barrier to accumulate in tumor sites. The hypoxia in TME can be relieved via O2 generated by MnO2 and the reactive oxygen species produced by Mn2+ can kill tumor cells. The tLyP-1-CD-DOPA-MnO2 @PTX nanoparticles exert a remarkable antitumor effect by promoting apoptosis and inhibiting proliferation of tumor cells in addition to enabling real-time tumor monitoring with magnetic resonance imaging. This MnO2 -based theranostic medicine will offer a novel strategy to simultaneously enhance chemotherapy and achieve real-time imaging of therapeutic process in glioma treatment.

Biogenic amine sensing and cancer detection in human urine based on a light-activated photocatalytic and pH-controlled probe

Development of novel biomarker and achievement of simple, sensitive, rapid and economical detection of cancer in clinic have become more urgent and indispensable. In this paper, a light-activated sensor, PMI-B, was developed. The selective sensing of BAs both in solution and in the PA membrane was achieved, especially for spermine. PMI-B exhibited selective sensing of BAs by a synergistic mechanism based on an autoacting photocatalytic mechanism and a pH-controlled deprotonation mechanism. Furthermore, the detection of cancer based on PMI-B with twenty-six human urine samples was investigated by UV–vis and fluorescence spectra. The ratio differences of A741/A561 and A741/A491 can effectively be used to classify breast cancer and other female cancer and lesion patients. Compared with the established tumor markers, the specificity of the A741/A516 value (the raw median value = 0.27) for PMI-B with various human urine samples was a potential malignant tumor marker for breast cancer patients.

Ubiquitination of ADRα1d/SerpinA1 complex stimulates hypoxia to induce gastric tumorigenesis with a combination of Helicobacter pylori and chronic stress through IL-1α.

Helicobacter pylori(H. pylori) has been recognized as the class I carcinogen of gastric cancerand several studies have demonstrated that chronic stress may accelerate gastric cancer progression.However, the evidence is not sufficient. Here, we developed a mouse model that combinedH. pyloriinfection with chronic stress. Gastric inflammation promotes gastric tumor development progression. To evaluate the number of pro-inflammatory cells through observing the numbers of activated macrophages and neutrophils in mice gastric tumors compared with untreated mice or only treated with one factor. ADRα1d /SerpinA1 expression and localization were assessed under stress conditions andH. pyloriinfection, and evaluated by analyzingIL-1α, CD8, platelet, and RBC status using α- or β- blockers against gastritis to prevent gastric cancer. Further mechanism study showed that stress hormones increase the number of CD8+lymphocytes by activating ADRβ2 receptors, leading to IL-1α secretion and tumorigenicity. Gastric carcinogenesis also involves gastric muscle contraction mediated through ADRα1d/Serpina1 interaction. Specifically, we showed that theADRα1d/SerpinA1 complex increases glucose uptake and the development of hypoxia conditions. These responses promote platelet aggregation and muscle contraction. In turn, gastric cancer cells increase lactate production and promote gastric cell proliferation through Muc-13 and IL-1α stimulation. H. pylori infection in combination with chronic stress can lead to gastric cancer, and the synergistic effects of cytokine production (i.e. IL-1α), T lymphocyte dysfunction contributes to gastric carcinogenesis which will offer treatment opportunities for stress-associated gastric cancer and provide new strategies for the prevention and treatment of gastric cancer in clinics.

The influence of the Covid-19 pandemic on the 90-day mortality rate after emergency surgery for colon cancer.

The Covid-19 pandemic had a significant impact on the treatment of colon cancer. This was due to the redistribution of doctors and medical resources to empower the treatment of Sars-CoV-2-infected patients. Moreover, the restrictions imposed by the authorities on the general population and hospitals were other key elements that had to be taken into consideration. The surgical activity was massively reduced for both elective and emergency surgeries during the pandemic; initially, the elective ones were postponed. This study aimed to analyze the impact of the Covid-19 pandemic on the 90-day postoperative mortality rate of patients who underwent emergency surgery for colon cancer in the First General Surgery Clinic of Pius Brinzeu County Hospital Timisoara. For conducting this study, data from patients who underwent emergency surgery for colon cancer between 26.02.2020–01.10.2021 and the same period of 2016–2017 and 2018–2019 were collected and analyzed, with a p<0.05 being considered statistically significant. As a result, the 90-days postoperative mortality rate increased to 34.5% during the pandemic. A 22.55% rate was observed during 2016–2017 and an 18.4% rate in 2018–2019. In addition, during the pandemic, correlations w ere identified between the presence of 90-day postoperative mortality and severe symptomatology when presenting to the hospital, stage of the disease, and Charlson comorbidity index. All these aspects influenced the 90-days mortality rate of patients undergoing emergency surgery to treat colon cancer during the pandemic.

Estrone-targeted PEGylated Liposomal Nanoparticles for Cisplatin (DDP) Delivery in Cervical Cancer

Cisplatin (DDP), a first-line chemo-drug for cervical cancer therapy, has limited the clinical use due to its high-dose administration and strong side effects. In this study, estrone-targeted PEGylated Liposomal DDP (ES-SSL-DDP) was prepared by thin-film hydration method and characterized. ES-SSL-DDP presented a spherical structure, with a particle size of about 97.3 nm, a surface charge of -19 mV and a high encapsulation efficiency of 47.7%. ES-SSL-DDP showed higher stability with a lower leakage rate less than 10% at 4°C. In vitro cellular uptake and internalization mechanisms in HeLa cells showed that ES-SSL-DDP had a stronger cellular uptake which was mainly via caveolin-mediated endocytosis. In vivo targeting evaluation demonstrated ES-SSL-DDP could specifically accumulated into the tumor site of HeLa-bearing mice. Cytotoxicity test on HeLa cells demonstrated the stronger cytotoxic activity of ES-SSL-DDP by MTT assay. In vivo anti-tumor efficacy of ES-SSL-DDP in HeLa tumor-bearing mice exhibited the most effective tumor inhibition. Pharmacokinetics and biodistribution of ES-SSL-DDP presented an improved metabolic behavior of the DDP. The acute toxicity demonstrated that ES-SSL-DDP could increase the LD50 and reduce the myelosuppression in healthy ICR mice. ES-SSL-DDP could be a novel promising chemo-formulation for cervical cancer in the future clinic.

Ultrasensitive “signal-on” sandwich electrochemiluminescence immunosensor based on Pd@Au-L-cysteine enabled multiple-amplification strategy for Apolipoprotein-A1 detection

In this work, a “signal on” electrochemiluminescence (ECL) strategy was proposed to detect Apolipoprotein-A1 (Apo-A1), a common tumor biomarker for bladder cancer. The tris(2,2′-bipyridyl)-ruthenium(II) [Ru(bpy)32+] was used as luminophor captured by three-dimensional (3D) zinc oxalate metal–organic frameworks (MOFs), which constructed as the ECL nanoprobe (Ru-MOF) for detecting Apo-A1. Meanwhile, L-cysteine (L-Cys) as the co-reactant was connected to the Pd@Au core–shell nanostructure through Au-S bond, which was directly modified on the glassy carbon electrode (GCE) to significantly reduce the electron transfer distance between the luminophor and co-reactant. The ECL intensity was “signal on” when the ECL probe of Ru-MOF was linked to the electrode by the immunoreaction of antigen–antibody. Based on these principles, the quantitative relationship between the concentration of Apo-A1 and the ECL intensity was obtained in the range of 1.00 fg·mL−1 to 1.00 ng·mL−1 with a linear coefficient of 0.9968. The proposed ECL immunosensor showed some great advantages, such as simplification, rapidity, stability and selectivity. It was also successfully applied for the determination of Apo-A1 in real serum and urine samples with the recovery of 98.0% ∼ 115.0% (RSD < 5.2%). To sum up, a “signal on” ECL immunosensor was successfully constructed for Apo-A1 detection, and it may facilitate the diagnosis of bladder cancer in clinic.

Prevalence of depression and anxiety among patients with breast cancer: a cross-sectional study

Background: Breast cancer patients have a significant rate of depression, according to prior studies. During some phases of patient management, particularly early after surgery, these patients are at risk for depression. Objectives: to assess the prevalence of depression and anxiety among patients with breast cancer and risk factors associated with it. Methods: This cross-sectional study enrolled 74 patients diagnosed with breast cancer in the general surgery clinic at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Two questionnaires were used, Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7), filled in by patients who attended the clinic or electronically by sending the questionnaires to the patients. Significant depression was defined as PHQ-9 score 10 and significant anxiety was defined as GAD-7 score 10. Sociodemographic and medical data were also collected. This research was approved by the unit of biomedical ethics at King Abdulaziz University Faculty of Medicine. Results: From the 74 patients with breast cancer, 36% of the women were found to have depression and 24% were found to have anxiety and the prevalence of having both depression and anxiety was 23.0%. Mean PHQ-9 score was (8.9, SD: 5.8). The mean GAD-7 score was (6.7, SD: 5.2). Significant depression and significant anxiety were found to be more in Saudi nationals, those who did not go for surgical therapy, patients with metastatic disease at the time of filling in the questionnaire and married women. These results were not statistically significant. Conclusion: This study showed that the prevalence of depression and anxiety was similar to previously conducted studies; it also showed no associations between the risk factors studied and anxiety or depression in patients with breast cancer. Keywords: Breast Cancer, depression, anxiety, Saudi Arabia, PHQ-9, GAD-7

The relationship between non-alcoholic fatty liver disease and breast cancer: a retrospective case-control study

Aim: Breast cancer is the most common cancer among women and is one of the main causes of death in women. It is known that some metabolic components that are risk factors for non-alcoholic fatty liver disease are also risk factors for breast cancer. The aim of this retrospective cohort study was to show the prevalence of non-alcoholic fatty liver disease breast cancer patients and the effect of non-alcoholic fatty liver disease on breast cancer development through comparisons with a control group with normal mammography. &#x0D; Material and Method: The study included 108 patients who were operated on for breast cancer in the general surgery clinic of our hospital between January 2015 and December 2018 and who underwent abdominal ultrasound for breast cancer staging. A control group was formed of 102 women with benign breast lesions on routine mammography and who underwent abdominal ultrasound within 6 months before mammography. The prevalence of diabetes, hypertension and hyperlipidemia and body mass indexes were similar in both groups. &#x0D; Results: In the evaluation of all the study participants, an association was found between non-alcoholic fatty liver disease and breast cancer. In the obese and non-obese subgroups, non-alcoholic fatty liver disease was significantly associated with breast cancer in the non-obese subgroup. [OR 2.67%, 95% confidence interval [95% CI) 1.1-6.0, p=0.020]. &#x0D; Conclusion: Non-alcoholic fatty liver disease was seen to be significantly associated with breast cancer regardless of known risk factors. This relationship there was in non-obese women with NAFLD, but not in the obese group.

Simultaneous enhancement of T1 and T2 magnetic resonance imaging of liver tumor at respective low and high magnetic fields.

Background: Nowadays, magnetic resonance imaging (MRI) is routinely applied in clinical diagnosis. However, using one contrast agent (CA) to simultaneously enhance the T1 and T2 MR contrast at low and high magnetic fields respectively has not been reported.Methods: Herein, we investigated the MR property of a γ-glutamyl transpeptidase (GGT)-instructed, intracellular formed gadolinium nanoparticle (DOTA-Gd-CBT-NP) at low and high magnetic fields.Results: Experimental results showed that DOTA-Gd-CBT-NP possesses a low r2/r1 ratio 0.91 which enables it to enhance T1 MR imaging of liver tumor at 1.0 T, and a high r2/r1 ratio 11.8 which renders the nanoparticle to largely enhance T2 MR imaging of liver tumor at 9.4 T.Conclusion: We expect that our GGT-responsive Gd-nanoparticle could be applied for simultaneous T1 and T2 MRI diagnosis of early liver cancer in clinic at respective low and high magnetic fields when the 9.4 T MR machine is clinically available in the future.

Mastektomi Sonrası Meme Kanserli Hastalarda Dren Alma Günü ile Meme Ağırlığı Arasındaki İlişki: Retrospektif Bir Çalışma

Objective: Surgeries performed for breast cancer often include wide flap practices and breast tissue resections. This condition paves the way for bothersome complications such as seroma, which negatively affect patient comfort and also require hospitalization. Hence, surgeons have adopted postoperative drain application as an indispensable routine. In this study, we aimed to examine the relationship between the weight of resected breast tissue after mastectomy and the postoperative drain removal time. Material and Methods: Retrospective medical records of 107 patients who underwent mastectomy procedures due to breast cancer in the surgical oncology clinic were exported from the hospital database. Statistical analyzes were performed within the confidence interval of 95%. A p value less than 0.05 was considered statistically significant. Results: The mean age of the patients was 55.13, mean body mass index was 28, mean day of drain removal was 8.45, mean number of lymph nodes removed was 12. Only 47% of the patients had metastatic lymph nodes, with an average of 4.6. We found that the time of drain removal was longer in patients who underwent modified radical mastectomy (MRM) and had axillary lymphatic involvement (p=0.00). In the correlation analysis performed, there was a positive correlation between postoperative drain removal time and breast weight (p=0.00), the total number of lymph nodes removed (p=0.00), number of metastatic lymph nodes (p=0.04), and body mass index (p=0.004). Conclusion: Our results are consistent with the current literature, and we recommend being more persistent for drainage practice in patients with axillary involvement, who are overweight and have large breast volumes, and not ignoring individual risks in clinical practice.

SPERT gene silencing inhibits the growth of human colon cancer xenograft tumor in nude mice via p38MAPK/HSP27 signaling pathway.

Colorectal cancer is one of the most common gastrointestinal malignancies and is also a disease of genetic heterogeneity. Our previous studies have shown that SPERT (sprermatid-associated protein) gene may be an underlying oncogene that is associated with the progression of the disease in colorectal cancer patients, and SPERT gene silencing can inhibit the proliferation of colorectal tumor cells and promote cell apoptosis. Here, we use the stably transfected human colorectal cancer cell line RKO to construct an animal xenograft model and study the effect of SPERT gene silencing on animal xenografts. The results showed that SPERT gene silencing can inhibit tumor growth in animals. In addition, through signaling pathway analysis, we found that the p38MAPK/HSP27 signaling pathway may be the molecular mechanism by which SPERT gene silencing inhibits the growth of xenograft tumors in nude mice. Combined with previous data, SPERT gene silencing has the same inhibitory effect on tumor growth in vitro and in vivo. These data suggest that SPERT gene may be a potential target for the treatment of colorectal cancer in clinic.

Amplifying antitumor T cell immunity with versatile drug delivery systems for personalized cancer immunotherapy

Cancer immunotherapy is becoming an important option for treating patients with cancer in clinic. Given the heterogeneity of tumors between individuals, personalized cancer immunotherapy is the most promising one. Tremendous progresses have been achieved to initialize personalized immunity in patients through delivering tumor-derived neoantigens or adoptive transfer of engineered immune cells such as T cells and nature killer cells. However, the objective response rate and therapeutic efficiency of most personalized immunotherapies are hampered by the biophysical barriers against drug delivery and the limited infiltration of engineered cells into solid tumors. To overcome these limitations, versatile drug delivery systems have been developed to deliver personalized tumor antigens to target and promote intratumoral infiltration of lymphocytes, thus generating a local immunogenic niche to induce potent and durable antitumor immune responses. In this review, we will summarize the major barriers for efficient personalized immunization, highlight our lab and several other groups’ efforts in versatile drug delivery systems for delivering tumor-specific antigens, autologous tumor cell-derived antigens and combining with adoptive transfer of engineered immune cells. At the end of this review, we also look forward to the future development of drug delivery system-based personalized immunotherapy and its challenges for clinical translation.

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer.

BackgroundChemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin.MethodsFour kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice.ResultsThe ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin.ConclusionIn this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.

SIOG2021-0087 - Impact of pharmacist-led medication reviews in older patients with cancer in an outpatient haematology clinic

SIOG2021-0087 - Impact of pharmacist-led medication reviews in older patients with cancer in an outpatient haematology clinic

Profile of molecular subtyping of breast cancer and clinicopathological features in Mankweng Hospital breast oncology clinic, Limpopo Province, South Africa.

Breast cancer is recognised as a heterogeneous disorder, comprising a number of subcategories of several cellular compositions, molecular alterations as well as clinical behaviour. Across the world, research has been able to show that the most common molecular subtype is luminal A, followed by triple negative and human epidermal receptor 2 (HER2)-positive (non-luminal) subtype. However, another study found that the most common molecular subtype was HER2/neu amplification, suggesting that subtypes case frequencies differ in different people. To determine the case frequency of molecular subtypes of breast cancers and the associated clinicopathological features in women from Limpopo Province, South Africa. We performed a retrospective, cross-sectional descriptive study from July 2021 - June 2021 at Mankweng Hospital breast oncology clinic. The inclusion criterion was all women with histologically confirmed breast cancer. We identified 222 women who met the inclusion criteria, and the age range (median) was 25 - 91 (54.8) years. The majority of the women came from the Vhembe district (28%; n=62), followed by Capricorn district (26%; n=59), Mopani district (17%; n=38), Sekhukhune district (16%; n=35), and Waterberg district (13%; n=28). Histology revealed that the most common type was invasive ductal carcinoma (no special type; 91.44%; n=203), followed by invasive mucinous carcinoma (4%; n=9). The most predominant molecular subtype was luminal B (48.19%; n=107), followed by luminal A (22.97%; n=51), triple negative (17.12%; n=38) and 11.75% (n=26) overexpressed HER2. More than one-third of the cancers were HER2-positive (40.54%; n=90), and 59.46% (n=132) were HER2-negative. The majority of patients presented with late-stage cancer (62.16%; n=138), and the rest presented with early-stage (I and II) disease (37.84%; n=84). The majority of our patients had luminal subtypes and hormonal receptor-positive breast cancers, which should be associated with very good clinical outcomes. However, the majority of patients presented late with advanced-stage disease and high Ki-67 expression. Therefore, research is required to help us understand why in our context patients present late with advanced-stage disease.

Coordination Polymer-Coated CaCO3 Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment.

Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO3 ) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.

Incidence and dynamic risk stratification in differentiated thyroid cancer in a high-resolution clinic, 2002–2017

ObjectiveWe evaluated the incidence, progression and the dynamic risk stratification in differentiated thyroid cancer (DTC) under follow-up in a high-resolution clinic (HRC). MethodsThis was a retrospective observational study on incident cases in the tumor registry from 2002 to 2017 and their evolution under follow-up in HRC. ResultsA total of 444 patients (78.5% women, 52.1±14.9 mean years old) were DTC diagnosed from 2002 to 2017. The incidence rate of DTC increased from 5.2 to 25.7×105 habitants/year in women and from 2.3 to 7.1×105 habitants/year in men (P<0.0001). This increased incidence was not associated with an increment in the incidental papillary microcarcinoma diagnosed (from 29.4% to 32%).In those patients undergoing follow-up at the HRC (84% papillary carcinomas), 65.7% were classified as being at a low risk of recurrence compared to 14.5% at high risk. Of those, 88.8% classified as making an excellent response at diagnosis remained disease-free at the final follow-up visit. However, those patients with an indeterminate or structurally incomplete response at diagnosis evolved to an excellent response in 55.8% and 42.9% of the cases, respectively, compared to 14.8% of those with a biochemically incomplete response (P<0.001) ConclusionsThe increased incidence of DTC is similar to results published previously in other countries. Dynamic risk stratification systems adequately classify DTC patients and assess diagnostic and treatment procedures, especially in low-risk subgroups.

Assessing Clinicopathological Features and Prognosis of Triple-Negative Breast Cancer Patients: A Single-Center Study in Turkey

Background: Triple-negative breast cancer (TNBC) is defined as tumors without estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. This cancer is associated with higher rates of recurrence risk when compared to other subtypes of breast cancers. In this study, we aimed to explore the basic clinicopathological characteristics, prognosis, and recurrence patterns of TNBC patients. Methods: In the current study, forty-five TNBC female patients operated on for breast cancer in the General Surgery Clinic of Kayseri City Training and Research Hospital between 2016 and 2021 were included and retrospectively evaluated. Results: The percentage of TNBC was 12% of the 502 breast cancer patients who could access all three pieces of receptor information. The mean age of the patients was 58.9±15.2 years (27-90), and the mean BMI was 30.4±5.17 (21.5-40.6). It was observed that the most common histological subtype was invasive ductal carcinoma, and at the time of diagnosis, 11 patients were stage 1 (24.4%), 31 patients were stage 2 (68.8%), 2 patients were stage 3 (4.4%), and 1 patient was stage 4 (2.2%). During the follow-up period, 11 patients (24,4%) developed metastasis and the most common sites were the brain and bones. The mean time from diagnosis to metastasis was 20.7±5.75 (12-29) months. The 3-year disease-free survival was 62%, and the 3-year overall survival (OS) was 70%. Conclusion: TNBCs are cancers with varying prevalence, poor prognosis, and limited treatment alternatives. The prevalence of TNBC in our center was found to be lower than the literature rates and consistent with the literature, the lymph node stage was related to poor OS and disease free survival (DFS).

Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell–related genes were identified. The drug–herb–active compound–target gene–disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.