Utilization and outcomes of the 21-gene recurrence score in de novo metastatic breast cancer.

BACKGROUND: Limited data exist regarding the utility and validity of the 21-gene recurrence score (RS) in patients with de novo metastatic breast cancer (dnMBC). This study aimed to investigate the practice patterns as well as associated survival outcomes based on 21-gene RS in dnMBC. RESEARCH DESIGN AND METHODS: The Surveillance, Epidemiology, and End Results Oncotype database was queried for women with hormone receptor-positive and Her2-negative dnMBC. RESULTS: A total of 153 patients were identified, including 62.7% and 37.3% of patients who had RS < 26 and ≥ 26, respectively. Patients with RS ≥ 26 were more likely to receive chemotherapy compared to those with RS < 26 (61.4% vs. 28.1%, p < 0.001). Patients with RS ≥ 26 had an inferior breast cancer-specific survival (BCSS) (2-year BCSS: 84.3% vs. 89.5, p = 0.067) and overall survival (OS) compared to those with RS < 26 (2-year OS: 76.9% vs. 87.4%, p = 0.018). The multivariate Cox proportional hazard models showed that those with RS ≥ 26 had a significantly inferior BCSS (hazard ratio [HR] 2.251, 95% confidence interval [CI] 1.056-4.799, p = 0.036) and OS (HR 2.151, 95%CI 1.123-4.120, p = 0.021) compared to those with RS < 26. CONCLUSIONS: The 21-gene RS assay is an important prognostic factor in patients with dnMBC.

A mitochondria-targeted multifunctional nanoplatform combining carbon monoxide delivery with O2-independent free radical burst under 1064 nm light irradiation for efficient hypoxic tumor therapy.

In situ mitochondrial oxidative stress amplification is an effective strategy to improve efficacy of cancer treatment. In this work, a tumor and mitochondria dual-targeted multifunctional nanoplatform CMS@AIPH@PDA@COTPP@FA (CAPCTF) was prepared, in which a thermally decomposable radical initiator AIPH was loaded inside the mesoporores of CuxMoySz (CMS) nanoparticles with polydopamine (PDA) covered films that were further covalently functionalized by a mitochondria-targeted CO donor (COTPP) and a directing group of folic acid (FA). The prepared CAPCTF nanoplatform selectively accumulated in cancer cells and further targeted the mitochondrial organelle where carbon monoxide (CO) and O2-independent free radicals (•OH/•R) were in situ generated upon 1064 nm laser irradiation. Furthermore, the CMS nanocarrier was capable of depleting the GSH overexpressed in the tumor microenvironment (TME), thus preventing free radical scavenging. As a result, the CAPCTF nanoplatform exhibited outstanding in vitro and in vivo antitumor efficacy under hypoxic conditions. This provides an innovative strategy that combines O2-independent free radicals (•OH/•R) generation, CO delivery and GSH consumption to amplify intracellular oxidative stresses and induce mitochondrial dysfunction, thus leading to cancer cells eradication, which may have significant implications for personalized hypoxic tumor treatment.

CircNCOR1 regulates breast cancer radiotherapy efficacy by regulating CDK2 via hsa-miR-638 binding.

BACKGROUND: Despite aggressive local and regional therapy, triple-negative breast cancer (TNBC) is characterized by an increased risk of locoregional recurrence. RNA-sequencing data has identified a large number of circRNAs in primary breast cancers, but the role of specific circRNAs in regulating the radiosensitivity of TNBC is not fully understood. This research aimed to investigate the function of circNCOR1 in the radiosensitivity of TNBC. METHODS: CircRNA high-throughput sequencing was conducted on two breast cancer MDA-MB-231 and BT549 cell lines after 6 Gy radiation. The relationship between circNCOR1, hsa-miR-638, and CDK2 was determined by RNA immunoprecipitation (RIP), FISH and luciferase assays. The proliferation and apoptosis of breast cancer cells were measured by CCK8, flow cytometry, colony formation assays, and western blot. RESULTS: Differential expression of circRNAs was closely related to the proliferation of breast cancer cells after irradiation. Overexpression of circNCOR1 facilitated the proliferation of MDA-MB-231 and BT549 cells and impaired the radiosensitivity of breast cancer cells. Additionally, circNCOR1 acted as a sponge for hsa-miR-638 to regulate the downstream target protein CDK2. Overexpression of hsa-miR-638 promoted apoptosis of breast cancer cells, while overexpression of CDK2 alleviated apoptosis and increased proliferation and clonogenicity. In vivo, overexpression of circNCOR1 partially reversed radiation-induced loosening of tumor structures and enhanced tumor cell proliferation. CONCLUSION: Our results demonstrated that circNCOR1 bounds to hsa-miR-638 and targets CDK2, thereby regulating the radiosensitivity of TNBC.

Pseudo-Meigs' syndrome secondary to breast cancer with ovarian metastasis: a case report and literature review.

Ovarian metastasis of breast cancer with pseudo-Meigs' syndrome (PMS) is extremely rare. Only four cases of PMS secondary to breast cancer with ovarian metastasis have been reported to date. In this report, we present the fifth case of PMS caused by ovarian metastasis of breast cancer. On the 2nd of July 2019, a 53-year-old woman presented to our hospital with complaints of abdominal distension, irregular vaginal bleeding, and chest distress. Color Doppler ultrasound examination revealed a mass approximately 109×89 mm in size in the right adnexal area, accompanied by multiple uterine fibroids and a large amount of pelvic and peritoneal effusions. The patient had no common symptoms and showed no signs of breast cancer. The main manifestations were a right ovarian mass, massive hydrothorax, and ascites. Lab workup and imaging revealed raised CA125 (cancer antigen 125) levels and multiple bone metastases. At first the patient was misdiagnosed with ovarian carcinoma. After the rapid disappearance of oophorectomy hydrothorax and ascites, and decreased CA125 levels, from 1,831.8u/ml to normal range. According to the pathology report, breast cancer was finally diagnosed. The patient underwent endocrine therapy (Fulvestrant) and azole treatment after oophorectomy. At the 40-month follow-up, the patient was still alive and doing well.

A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy.

A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn2+ further catalyzed the decomposition of endogenous H2O2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy.

The addition of radiotherapy to breast-conserving surgery improves survival for elderly patients with early breast cancer.

Purpose: To evaluate whether adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) was associated with better survival among elderly (≥70 years) breast cancer patients with T1-2N0 and estrogen receptor (ER) positive disease. Methods: We included patients who met the inclusion criteria between 2010 and 2014 from the Surveillance, Epidemiology, and End Results program. Patients were subdivided into three groups based on surgery and RT: BCS alone, BCS plus RT, and refusal of RT. The primary outcomes were breast cancer-specific survival (BCSS) and overall survival (OS). Chi-squared tests, Kaplan-Meier method, and Multivariate Cox regression analysis were used for statistical analysis. Propensity score matching (PSM) was performed to minimize the potential selection bias. Results: A total of 26586 patients were included in this analysis. The median follow-up was 66 months. Of these patients, 15591 (58.6%) patients received RT, RT was recommended but not performed due to patient refusal for 1270 (4.8%) patients, and RT was not recommended for 9725 (36.6%) patients. The 5-year BCSS was 98.3% for patients receiving RT, 97.1% for patients refusal of RT, and 96.4% for patients not recommended RT (P<0.001). The 5-year OS was 88.6% for patients receiving RT, 77.6% for patients who refused RT, and 72.1% for patients not recommended RT (P<0.001). Multivariate Cox regression analyses showed that patients who received adjuvant RT after BCS had significantly better BCSS (hazard ratio [HR] 0.523, 95%confidence interval [CI] 0.447-0.612, P<0.001) and OS (HR 0.589, 95%CI 0.558-0.622, P<0.001) compared to those without RT. A total of 7721 pairs of patients were matched successfully between those with and without RT using PSM. The results also showed that patients who received RT after BCS had significantly better BCSS (HR 562, 95%CI 0.467-0.676, P<0.001) and OS (HR 0.612, 95%CI 0.0.575-0.652, P<0.001) compared to those without RT. Conclusions: These data suggest that individual counseling is important for treatment decision-making in elderly breast cancer patients with T1-2N0 and ER-positive disease. Given the relatively lower toxicity of modern RT techniques, adjuvant RT should be recommended in patients with high life expectancy.

The Prognostic and Predictive Effects of Human Papillomavirus Status in Hypopharyngeal Carcinoma: Population-Based Study.

BACKGROUND: The role of the Human Papillomavirus (HPV) status in patients with hypopharyngeal squamous cell carcinoma (HSCC) remains controversial. OBJECTIVE: Our aim was to determine the prognostic and predictive effects of HPV status in patients with locally advanced HSCC (stage III-IVB) receiving primary radiotherapy. METHODS: Patients diagnosed with stage III-IVB HSCC between 2010 and 2016 were identified. HPV status, demographics, clinicopathological characteristics, treatment, and survival data were captured. Kaplan-Meier analysis, multivariable Cox regression analysis, and propensity score matching analysis were performed. RESULTS: We identified 531 patients in this study and 142 (26.7%) patients with HPV-positive diseases. No significant differences were observed between those with HPV-negative and HPV-positive diseases with regard to demographics, clinicopathological characteristics, and chemotherapy use. HPV-positive HSCC had better head and neck cancer-specific survival (HNCSS; P=.001) and overall survival (OS; P<.001) compared to those with HPV-negative tumors. Similar results were found using the multivariable Cox regression analysis. Sensitivity analyses showed that the receipt of chemotherapy was associated with significantly improving HNCSS (P<.001) and OS (P<.001) compared to not receiving chemotherapy in HPV-negative HSCC, whereas comparable HNCSS (P=.59) and OS (P=.12) were found between both treatment arms in HPV-positive HSCC. Similar results were found after propensity score matching. CONCLUSIONS: Approximately one-quarter of HSCC may be HPV-related, and HPV-positive HSCC is associated with improved survival outcomes. Furthermore, additional chemotherapy appears to be not related to a survival benefit in patients with HPV-positive tumors who received primary radiotherapy.

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

Purpose: To assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis. Methods: Using linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazard model were used for analyses. Results: Among the 3,036 long-term NPC survivors, 1,432 survived for >5-10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years. Conclusions: The probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.

A multifunctional nanoplatform delivering carbon monoxide and a cysteine protease inhibitor to mitochondria under NIR light shows enhanced synergistic anticancer efficacy.

Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, which was capable of mitochondria-targeted co-delivery of the cysteine protease inhibitor and carbon monoxide (CO) stimulated with an 808 nm near infrared (NIR) laser. Nanoplatform (1) was prepared by covalent attachment of a mitochondria-targeted CO donor (TPPMnCO) and a Ru(II)-caged cysteine protease inhibitor (Ru-inhibitor) on the surface of fluorescent N-doped graphene quantum dots (N-GQDs). Nanoplatform (1) preferentially accumulated in the mitochondria of cancer cells and instantly delivered CO and the cysteine protease inhibitor upon 808 nm NIR light irradiation, thus damaging mitochondria and leading to significant in vitro and in vivo anticancer efficacy. In addition, nanoplatform (1) has good biocompatibility and did not exert any toxic side effects on mice during the period of treatment. The targeted subcellular mitochondrial co-delivery of CO and the cysteine protease inhibitor may provide new insights into CO and enzyme inhibitor combined therapies for cancer treatment.

The Predictive Effect of the 8th AJCC Pathological Prognostic Staging on the Benefit of Postmastectomy Radiotherapy in N2/N3 Breast Cancer.

Background: The role of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on treatment-decision making of breast cancer (BC) remains unclear. This study aimed to investigate the predictive effect of the 8th AJCC PPS on the benefit of postmastectomy radiotherapy (PMRT) in N2/N3 BC. Methods: We included women with stage N2/3 BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. The effect of PMRT on breast cancer-specific survival (BCSS) was evaluated using the multivariate Cox proportional-hazards models. Results: A total of 13,445 patients were identified, including 10,547 (78.4%) patients treated with PMRT. All patients had reassigned stages based on the 8th AJCC PPS. There were 7102 patients (52.8%) that had stage changed, including 1160 patients (8.6%) were upstaged and 5942 patients (44.2%) were downstaged from the 7th AJCC anatomical staging (AS) to the 8th AJCC PPS. Regarding the 7th AJCC AS, 7603 (56.5%), 948 (7.1%), and 4895 (36.4%) were stage IIIA, IIIB, and IIIC diseases, respectively. Using the 8th AJCC PPS, 3525 (26.2%), 460 (3.4%), 1335 (9.9%), 3457 (25.7%), 2169 (19.1%), and 2100 (15.6%) patients were restaged as IB, IIA, IIB, IIIA, IIIB, and IIIC diseases, respectively. The PPS displayed increased prognostic accuracy and improved model fit with respect to BCSS compared to the 7th AS (C-index, 0.731 vs 0.605, P < 0.001; Akaike Information Criterion, 42141 vs 43118). Regarding the AS, the receipt of PMRT was associated with a better BCSS in those with stage IIIA (P = 0.004), IIIB (P = 0.003), and IIIC (P < 0.001) diseases. Using the PPS, the receipt of PMRT was not associated with a better BCSS among patients with stage IB (P = 0.446), IIA (P = 0.140), and IIB (P = 0.248) disease, while the receipt of PMRT was associated with a better BCSS for those with stage IIIA (P = 0.009), IIIB (P < 0.001), and IIIC (P < 0.001) disease. Conclusion: The 8th AJCC staging provides superior risk stratification and a better tool to predict the benefit of PMRT in N2/3 BC.

The prognostic effect of residual tumor for advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy or primary debulking surgery.

PURPOSE: The role of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC) remains controversial. This study aimed to investigate the prognosis between NACT and PDS in advanced EOC. We also investigated the prognostic effect of the residual tumor (RT) after NACT and PDS. METHODS: Patients with stage III-IV EOC diagnosed between 2010 and 2017 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, multivariate logistic regression analysis, Kaplan-Meier curves, and Cox proportional hazards model were used for statistical analyses. RESULTS: A total of 5522 women patients were identified, 2017 (36.5%) and 3505 (63.5%) patients received NACT and PDS, respectively. There were 2971 (53.8%), 1637 (29.6%), and 914 (16.6%) patients who had no residual tumor, RT ≤1 cm, and RT >1 cm, respectively. There were 25.5% of patients receiving NACT in 2010 and 48.4% in 2017 (p < 0.001). Women treated with NACT were not related to a higher chance of complete resection than the PDS group (p = 0.098). Patients receiving PDS had significantly better cancer-specific survival (CSS) than those receiving NACT (p < 0.001). The 5-year CSS was 35.3% and 51.1% in those receiving NACT and PDS, respectively. In patients receiving NACT, those who had no residual tumor had significantly better CSS compared to those who had RT ≤1 cm (p < 0.001), while comparable CSS was found between those who had RT ≤1 cm and RT >1 cm (p = 0.442). In those receiving PDS, the CSS was decreased with a RT increase (p < 0.001). CONCLUSIONS: Our study suggests that PDS may be the optimal procedure for the majority of advanced EOC patients. Complete resection of all residual diseases should be the goal with the increased utilization of NACT.

Distribution, Chemotherapy Use, and Outcome of the 21-Gene Recurrence Score Between Chinese and White breast Cancer in the United States.

PURPOSE: To compare the distribution, chemotherapy-decision making, and prognosis of the 21-gene recurrence score (RS) between Chinese breast cancer (BC) in the United States and White American (WA) BC. METHODS: We identified early-stage and estrogen receptor-positive BC patients diagnosed between 2004 and 2015. Multivariate logistic regression, Kaplan-Meier analysis, and multivariate Cox proportional hazards models were used for statistical analyses. RESULTS: A total of 67,486 patients were identified, including 66,215 (98.1%) WA patients and 1271 (1.9%) Chinese patients. Regarding the RS, 38,894 (57.6%) had low RS, 23,882 (35.4%) had intermediate RS, and 4710 (7.0%) had high RS. A similar distribution of RS was found between WA and Chinese BC (P = .280). The race was not the predictor associated with high RS. Similar trends of chemotherapy use were found in Chinese and WA BC. In WA BC, there were 4.1%, 31.5%, and 72.2% of patients receiving chemotherapy in low, intermediate, and high RS cohorts, respectively (P < .001). The proportion of chemotherapy use was 6.8%, 30.9%, and 74.0% in Chinese BC with low, intermediate, and high RS cohorts, respectively (P < 0.001). The multivariate prognostic analyses indicated that a higher RS was independently associated with an inferior breast cancer-specific survival. Similar trends were found among those with Chinese and WA BC. CONCLUSION: Our results demonstrate similar distribution, chemotherapy use, and outcome of the 21-gene RS between Chinese and WA BC in the United States.

NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy.

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

Long-Term Survival Among Histological Subtypes in Advanced Epithelial Ovarian Cancer: Population-Based Study Using the Surveillance, Epidemiology, and End Results Database.

BACKGROUND: Actual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported. OBJECTIVE: This study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC. METHODS: We performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model for the analyses. RESULTS: We included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer-specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors. CONCLUSIONS: Ovarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.

Biopsy of cervical lymph node does not impact the survival of nasopharyngeal carcinoma.

PURPOSE: The optimal practice regarding cervical lymph node biopsy (CLNB) remains to be defined to provide the best clinical management in nasopharyngeal carcinoma (NPC). This study aimed to investigate the effect of CLNB on the survival of NPC patients. METHODS: Patients diagnosed with NPC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression, Kaplan-Meier method, Cox proportional hazards regression analysis, and propensity score matching (PSM) were used to determine the factors associated with CLNB and prognostic effect of CLNB of NPC. RESULTS: We included 1903 patients in this study. There were 321 (16.9%) and 1582 (83.1%) patients with and without CLNB, respectively. The percentage of CLNB was 19.4% in 2004 and was decreased to 8.6% in 2015 (p = 0.044). Patients diagnosed in later years (p = 0.008), older age (p < 0.001), Chinese (p = 0.002), advanced tumor stage (p < 0.001), and early nodal stage (p = 0.003) were less likely to receive additional CLNB. In patients who received additional CLNB, the 5-years NPC-specific survival (NPCSS) was 83.6%, which was similar to patients without CLNB (80.1%, p = 0.159). In addition, a similar 5-years NPCSS was found between those receiving biopsy or aspiration of regional lymph node and those receiving lymph node resection (p = 0.584). There were 187 pairs of patients who were completely matched using PSM, the multivariate prognostic analyses indicated that the receipt of CLNB was not associated with an inferior outcome in the PSM cohort (p = 0.349). Similar results were found after stratification by the year of diagnosis, race/ethnicity, and histology. CONCLUSION: Additional CLNB is not associated with an inferior survival outcome in NPC. Our study provides a reference for the clinical practice of NPC.

[Genetic Polymorphism of Antigens in Twelve Rare Blood Group Systems of Li Nationality in Hainan Province].

OBJECTIVE: To explore the distribution characteristics of main antigen gene frequencies of Duffy,Diego,Kidd,Dombrock,MNS,Lutheran,Kell,Colton,Scianna,Yt,Knops and Indian in red blood cell blood group system of Li nationality in Hainan Province. METHODS: Antigens in twelve rare blood group systems of 214 Li people in Hainan Province were genotyped and analyzed by polymerase chain reaction-sequence specific primers (PCR-SSP). RESULTS: The gene frequency of antigens in twelve rare blood group systems of 214 Li people in Hainan Province including: the gene frequency of Duffy blood group system: fya=0.9556，fyb=0.0444；the gene frequency of Diego blood group system: Dia=0.0678，Dib=0.9322；the gene frequency of Kidd blood group system：JKa=0.4533，JKb=0.5467；the gene frequency of Dombrock blood group system：DOa=0.1051，DOb=0.8949；the gene frequency of MNS blood group system：M=0.8131，N=0.1869,S=0.0327，s=0.9673，Mur+=0.5748，Mur-=0.4252；the gene frequency of Lutheran blood group system：AUa=0.8318，AUb=0.1682；the Kell, Colton, Scianna, Yt, Knops and Indian blood type systems showed a monomorph and the genotype was kk, coacoa, Sc1Sc1, YtaYta, KnaKna and InbInb. The observed and expected genotype values in twelve rare blood group systems of Li nationality in Hainan province were obeyed by the Hardy-Weinberg genitic rules. The difference between the observed and expectated values of the Kidd blood group system showed significant differences（χ2=17.1946，P=0.0002）. CONCLUSION: The genetic distribution and genetic status in twelve rare blood group systems of Li nationality in Hainan Province are relatively stable. The gene distribution of Duffy, Diego, Kidd, Drombrock, MNS and Lutheran blood group systems are polymorphic and show unique distribution characteristics compared with other regions and different nationalities. The gene frequency distribution of Kell、Colton、Scianna、Yt、Knops、Indian blood group systems are monomorphic.

Mitochondria-targeted carbon monoxide delivery combined with singlet oxygen production from a single nanoplatform under 808 nm light irradiation for synergistic anticancer therapy.

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BACKGROUND: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. METHODS: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. RESULTS: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis. CONCLUSIONS: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.

Adjuvant chemotherapy and survival outcome in node-negative breast cancer with a 21-gene recurrence score of 26-30.

Aim: To investigate the benefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scores of 26-30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patients received adjuvant chemotherapy. Patients with higher tumor grade, larger tumors and younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patients without chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated or undifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26-30, especially for patients with high-grade tumors.

Lay abstract In current clinical practice, the 21-gene recurrence score has been developed for chemotherapy decision-making based on prognostic risk stratification, especially for patients with tumor size ≤5 cm, node-negative, hormone receptor-positive and HER2-negative breast cancer. However, the chemotherapy benefit in breast cancer patients with a 21-gene recurrence score (RS) of 26­30 is unclear. This study aimed to investigate the survival benefit of additional chemotherapy for early-stage breast cancer patients with RS 26­30 using the Surveillance, Epidemiology, and End Results data. Our study suggests that the RS 26­30 group is regarded as a uniform entity by clinicians. Adjuvant chemotherapy improves the outcome for early-stage breast cancer patients with RS 26­30, especially for patients with high-grade tumors.

Visible light-controlled carbon monoxide delivery combined with the inhibitory activity of histone deacetylases from a manganese complex for an enhanced antitumor therapy.

Multifunctional drugs with synergistic effects have been widely developed to enhance the treatment efficiency of various diseases, such as malignant tumors. Herein, a novel bifunctional manganese(I)-based prodrug [MnBr(CO)3(APIPB)] (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl)benzamide) with inhibitory histone deacetylase (HDAC) activity and light-controlled carbon monoxide (CO) delivery was successfully designed and synthesized. [MnBr(CO)3(APIPB)] readily released CO under visible light irradiation (λ > 400 nm) through which the amount of released CO could be controlled by manipulating light power density and illumination time. In the absence of light irradiation, the cytotoxic effect of [MnBr(CO)3(APIPB)] on cancer cells was greater than that of the commercially available HDAC inhibitor MS-275. Consequently, with a combination of CO delivery and HDAC inhibitory activity, [MnBr(CO)3(APIPB)] showed a remarkably enhanced antitumor effect on HeLa cells (IC50 = 3.2 µM) under visible light irradiation. Therefore, this approach shows potential for the development of medicinal metal complexes for combined antitumor therapies.