Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool.

Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.

Hippo cooperates with p53 to maintain foregut homeostasis and suppress the malignant transformation of foregut basal progenitor cells.

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of Mst1/2 in mice leads to epithelial overgrowth in both the esophagus and forestomach. Further molecular studies find that Mst1/2-deficiency promotes epithelial growth by enhancing basal cell proliferation in a Yes-associated protein (Yap)-dependent manner. Moreover, Mst1/2 deficiency accelerates the onset of foregut SCC in a carcinogen-induced foregut SCC mouse model, depending on Yap. Significantly, a combined deletion of Mst1/2 and p53 in basal progenitor cells sufficiently drives the initiation of foregut SCC. Therefore, our studies shed light on the collaborative role of Hippo signaling and p53 in maintaining squamous epithelial homeostasis while suppressing malignant transformation of basal stem cells within the foregut.

Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition.

The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.

Ferroptosis as a promising therapeutic strategy for melanoma.

Malignant melanoma (MM) is the most common and deadliest type of skin cancer and is associated with high mortality rates across all races and ethnicities. Although present treatment options combined with surgery provide short-term clinical benefit in patients and early diagnosis of non-metastatic MM significantly increases the probability of survival, no efficacious treatments are available for MM. The etiology and pathogenesis of MM are complex. Acquired drug resistance is associated with a pool prognosis in patients with advanced-stage MM. Thus, these patients require new therapeutic strategies to improve their treatment response and prognosis. Multiple studies have revealed that ferroptosis, a non-apoptotic form of regulated cell death (RCD) characterized by iron dependant lipid peroxidation, can prevent the development of MM. Recent studies have indicated that targeting ferroptosis is a promising treatment strategy for MM. This review article summarizes the core mechanisms underlying the development of ferroptosis in MM cells and its potential role as a therapeutic target in MM. We emphasize the emerging types of small molecules inducing ferroptosis pathways by boosting the antitumor activity of BRAFi and immunotherapy and uncover their beneficial effects to treat MM. We also summarize the application of nanosensitizer-mediated unique dynamic therapeutic strategies and ferroptosis-based nanodrug targeting strategies as therapeutic options for MM. This review suggests that pharmacological induction of ferroptosis may be a potential therapeutic target for MM.

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy.

While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

Clinical research of the value of high-risk CTV setting on intensity-modulated radiotherapy for stage IIB-IVA cervical cancer.

BACKGROUND: This study aims to evaluate the clinical efficacy and side effects of setting up a high-risk clinical target volume (CTV-hr) alongside simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) in patients diagnosed with stage IIB-IVA cervical cancer. METHODS: This study retrospectively analysed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University between November 2014 and September 2019. The patients were divided into experimental and control groups based on whether CTV-hr was set. All patients received a combined treatment of radiotherapy and chemotherapy. The dosage for paclitaxel was 135 mg/m2, while for cisplatin it was 75 mg/m2 or for carboplatin it was AUC 4-6, given in a cycle of 21 days. Radiotherapy (RT) included external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). In the control group, positive lymph nodes (GTV-n) were treated at a dose of 58-62 Gy/26-28 fractions(f), while clinical target volumes (CTV) were treated with a dose of 46-48 Gy/26-28f. The experimental group received a simultaneous integrated boost (SIB) to CTV-hr at a dose of 54-56 Gy/26-28f, with the same CTV and GTV-n as the control group. Both groups were combined with brachytherapy with a total dose (EQD2, the equivalent dose in 2 Gy/f) of 80-90 Gy. The study measured objective remission rate (ORR), 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, recurrence rate, and side effects as endpoints. RESULTS: The study enrolled 217 patients, with 119 in the experimental group and 98 in the control group. Results showed that the experimental group had a higher 3-year OS rate (87.4% vs. 71.4%, p = 0.001) and 3-year PFS rate (72.3% vs. 51.0%, p = 0.000) compared to the control group. Additionally, the experimental group had significantly lower rates of overall recurrence (26.1% vs. 50.0%, p = 0.003), in-field recurrence (15.1% vs. 36.7%, p = 0.000), and out-field recurrence(13.4% vs. 35.7%, p = 0.000) compared to the control group. All observed differences were found to be statistically significant. However, the experimental and control groups had no statistically significant difference in ORR and radiological side effects, such as radiation cystitis and enteritis (p > 0.05). CONCLUSIONS: Setting CTV-hr and performing IMRT-SIB on patients with stage IIB-IVA cervical cancer effectively increased the 3-year OS rate, 3-year PFS rate and reduced recurrence rate, with no significant differences in side effects.

Camrelizumab combined with anlotinib for the treatment of small cell lung cancer: a case report and literature review.

Data in 2020 show that lung cancer is the second most common cancer with the highest morbidity and mortality in the world, among which small cell lung cancer (SCLC) accounts for about 15% of the total number of lung cancers, but the number of deaths accounts for 25% of lung cancers. SCLC is an aggressive malignancy disease with a high recurrence rate and poor prognosis. The survival rate of small cell lung cancer is lower than other types of lung cancer and the prognosis is very poor. At present, there is still a lack of effective therapeutic options for SCLC after the failure of second-line treatment. However, studies have shown that anti-vascular therapy and programmed death-1 (PD-1) inhibitors are effective in SCLC. In the present case, a combination therapy of camrelizumab, a PD-1 inhibitor, and anlotinib (an anti-angiogenic drug) was administered to treat a 58-year-old male patient with programmed cell death-Ligand 1 (PD-L1) negative metastatic SCLC accompanied by primary tongue cancer. A total of 28 cycles were used from March 2020 to November 2021. Until November 2021, the survival time of the patient is 31 months; he has survived for 19 months with no disease progression, and is currently classified as complete response (CR). Our study demonstrates that camrelizumab plus anlotinib may be a promising treatment option for patients with metastatic SCLC.

Clinicopathological and therapeutic analysis of primary breast squamous cell carcinoma.

BACKGROUND: Primary squamous cell carcinoma (PSCC) of the breast is a rare type of breast cancer that exhibits unique biological behavior. The pathogenesis, clinical manifestations, and effective treatment methods of this breast cancer are still unclear. METHODS: We collected all breast PSCC patients who were treated in our hospital from June 2010 to December 2018 for retrospective analysis. The clinical, pathological, treatment, and prognostic characteristics of all patients were described and compared to past breast PSCC data, to provide advice on the diagnosis and treatment for breast PSCC. RESULTS: We identified 35 patients with breast PSCC treated at our hospital during this period. Preoperative ultrasound showed cystic hypoechoic nodules and abundant blood flow signals in 83.33% of the cases. Postoperative pathology showed that the average diameter of the breast mass was 27.51 mm, and 34.29% of the patients had poor differentiation. A total of 33 patients had negative expression of estrogen receptor (ER) and progesterone receptor (PR), and 32 patients had no overexpression of human epidermal growth factor receptor 2 (HER2). The average follow-up time was 36.29 months. There were 3 cases of local recurrence, 2 cases of distant metastasis, and 1 case of natural death. CONCLUSIONS: Breast PSCC has a special biological behavior. Surgery is the main treatment, platinum-containing chemotherapy may be more effective for breast PSCC. Radiotherapy can reduce local recurrence, but the scope and dose of radiotherapy need to be further confirmed.

Camrelizumab for the treatment of advanced cervical adenocarcinoma: a case report and literature review.

Cervical adenocarcinoma belongs to an invasive subtype of cervical carcinoma, presenting poorly prognostic status. Chemotherapy treatment for recurrent cervical carcinoma are thought to be limited and supposed to be noncurative. Because of the poor prognosis of patients with recurrent cervical carcinoma, however, the benefits of second-line chemotherapy have not yet reached a consensus. Immunotherapy is a split-new tactic of overwhelming carcinomas that relies on the instinct of the immune system to recognize and directly kill neoplasm cells. Here, we reported a 55-year-old female patient with clinical stage IVB cervical adenocarcinoma. The patient received four cycles of systematic therapy, with the regimen of docetaxel plus carboplatin in combined with bevacizumab anti-vascular therapy. The progressive disease (PD) was assessed by imaging evaluation and PD was confirmed once more after four cycles of chemotherapy of albumin paclitaxel plus cisplatin. The patient exhibited a good response during the twelve-cycle of immunotherapy of Camrelizumab, whereas PD was observed upon termination of her immunotherapy. This case with the treatment of PD-1 inhibitor Camrelizumab exhibits a good curative effect and tolerable adverse reactions. In addition, some clinical markers and biomarkers expression levels can be served as the predictors of the effect of anti-PD-1 immunotherapy.

Primary squamous cell carcinoma of the breast: A case report and review of the literature.

Primary squamous cell carcinoma (PSCC) of the breast, as a rare metaplastic breast cancer, currently has limited clinical data on its biological behavior, treatment and prognosis. At present, the optimal treatment of this tumor is still controversial. We reported a case of a 56-year-old woman with a mass on the right breast. She underwent a modified radical mastectomy and lymph node biopsy, which revealed that the tumor was a metaplastic squamous cell carcinoma with axillary lymph node metastasis, followed by traditional adjuvant chemotherapy and radiotherapy. The patient re-examined by PET/CT after two years in May 2017 and found a recurrence in the right chest wall, so resection of the recurring lesion was resected, then she was given postoperative adjuvant radiotherapy and chemotherapy. In August 2019, the patient re-examined by PET/CT, and there were pulmonary and mediastinal lymph node metastases. After 4 cycles of albumin paclitaxel plus cisplatin chemotherapy combined with nivolumab immunotherapy, the patient achieved complete response (CR), and then switched to nivolumab immune maintenance therapy. So far, no obvious metastasis has been seen. We believe that surgical treatment is necessary for PSCC of the breast;paclitaxel and cisplatin chemotherapy regimens and adjuvant radiotherapy are effective, but it may be resistant to radiotherapy; and immunotherapy may prolong the survival of patients with PSCC of the breast.

Efficacy and safety of nimotuzumab combined with chemoradiotherapy in the treatment of locally advanced cervical cancer.

Background: Platinum-based concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer (LACC). Improving the efficacy of LACC treatment is the focus of clinical research, and nimotuzumab combined with CCRT is a new research direction. This retrospective study aimed to investigate the efficacy and safety of nimotuzumab combined with CCRT compared with CCRT alone for treating LACC. Methods: Data from LACC patients treated at The Affiliated Hospital of Qingdao University from March 2017 to December 2019 were collected, and patients were assigned to either a nimotuzumab plus chemoradiotherapy (N + CCRT) group or a CCRT group. Baseline data were also collected. Patients were followed up every 3 to 6 months by imaging examination or telephone. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were complete response rate (CRR), objective response rate (ORR), and incidence of adverse events (AEs). Results: A total of 120 patients (65 in the N + CCRT group and 55 in the CCRT group) were enrolled, which baseline data were no statistical difference between the two groups (P>0.05). In the N + CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 98.46%, 95.38%, and 90.50%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 89.23%, 83.08%, and 79.73%, respectively. The CRR was 86.15% (56/65), and the ORR was 92.31% (60/65). In the CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 94.55%, 87.27%, and 78.18%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 81.82%, 69.09%, and 59.69%, respectively. The CRR was 70.91% (39/55), and the ORR was 87.27% (48/55). The CRR (86.15% vs. 70.91%, P=0.040) and 3-year cumulative PFS rates (79.73% vs. 59.69%, P=0.039) were significantly higher in the N + CCRT group than in the CCRT group. The incidences of various AEs were from 5.45% to 95.38%, without significant difference in AEs between the two groups (P>0.05). Conclusions: Nimotuzumab combined with CCRT enhanced the PFS and CRR of LACC patients and was well tolerated. The results can provide reference for clinical treatment of LACC.

LncRNA PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis by miR-153-3p/GRB2 axis via ERK/p38 pathway.

BACKGROUND AND AIMS: LncRNA plasmacytoma variant translocation 1 (PVT1) plays a regulatory role in some cardiovascular diseases, but its role in atherosclerosis (AS) remains barely explored. The study aimed to investigate the effects of PVT1 on high fat diet-induced AS and its potential mechanisms. METHODS AND RESULTS: ApoE -/- mice were fed with high fat diet for 8 weeks to establish an AS model. Lentiviral vectors containing PVT1 short hairpin RNA (PVT1-shRNA) or NC-shRNA were administered by tail vein injection. Cell viability, apoptosis, inflammatory factor secretion, and cellular oxidative stress were measured to evaluate oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm the interaction between miR-153-3p and PVT1 or growth factor receptor binding protein 2 (GRB2). Atherosclerotic lesions, lipid deposition, and cell apoptosis in aorta were analyzed by H&E, Oil Red O, and TUNEL straining. PVT1 knockdown alleviated ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs. PVT1 acted as a sponge of miR-153-3p, and GRB2 was confirmed as a target of miR-153-3p. MiR-153-3p overexpression attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage. GRB2 overexpression reversed the mitigating effects of miR-153-3p on ox-LDL-caused injury. Inhibiting PVT1 restrained the activation of ERK1/2 and p38 pathway via miR-153-3p/GRB2 axis. Additionally, silencing PVT1 in vivo reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress, and apoptosis in AS mice. CONCLUSION: PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway.

The efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND: This study aimed to evaluate efficacy and adverse effects of different radiotherapy (RT) doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer. METHODS: Fifty-nine patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy in hospital between January 2015 and May 2017 were enrolled in retrospective analysis. The patients were divided into the 56-Gy group and the 50-Gy group. The concurrent chemotherapy regimen was based on capecitabine. All patients received one cycle of oxaliplatin combined with capecitabine induction chemotherapy. All patients completed neoadjuvant chemoradiotherapy and received radical surgery. RESULTS: Of the patients in this study, 29 patients and 30 patients received a radiation dose of 56- and 50-Gy, respectively. All clinical characteristics were matched between the two groups. All patients received surgery 6 to 8 weeks after completing RT. The therapeutical effective rate in the 56-Gy group was 93.10% (27/29), compared with 66.67% in the 50-Gy group (20/30); the difference between the two groups was statistically significant (χ2=6.36, P=0.01). The pathological complete remission (pCR) rate in the 56-Gy group (37.93%, 11/29) was statistically significantly higher than that in the 50-Gy group (13.33%, 4/30) (χ2=4.71, P=0.030). The anal preservation rate in the 56-Gy group (65.5%, 19/29) was statistically significantly higher than that in the 50-Gy group (33.33%, 10/30) (χ2=6.11, P=0.01). The 56-Gy group had a local recurrence rate of 0% (0/29) and a distant metastasis rate of 10.34% (3/29), while the 50-Gy group had a local recurrence rate of 6.67% (2/30) and a distant metastasis rate of 16.67% (5/30); no significant difference existed between the two groups (χ2=2.00, 0.50, P=0.16, 0.48). The incidence of adverse reactions (gastrointestinal reactions, bone marrow suppression, and perianal skin reactions) in the 56-Gy group was not significantly different from that in the 50-Gy group (P>0.05). CONCLUSIONS: Increasing the radiation dose can significantly improve the anal preservation and pCR rates of patients with locally advanced rectal cancer, thus improving their life quality. Moreover, it does not increase the rates of recurrence or adverse reactions. Our findings have certain clinical significance, but further prospective study is needed.

Clinical outcomes observation in stage IIB-IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy.

BACKGROUND: To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB-IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery. METHODS: Forty-nine patients diagnosed with stage IIB-IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. RESULTS: Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 and P = 0.044, respectively). CONCLUSION: CCRT combined with surgery for stage IIB-IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy.

The relentless debate on postoperative adjuvant radiotherapy in gastric adenocarcinoma (GA) has been lasting for decades. In this study, a new biomarker, named promoter methylation burden of DNA repair genes (RPMB), was established to identify the subgroup of patients who might benefit from adjuvant radiotherapy. Methylation profiles of 397 GA tumor samples were downloaded from The Cancer Genome Atlas (TCGA). RPMB for a patient was defined as the ratio of methylated DNA repair genes to the number of all DNA repair genes. Subgroup analyses in term of overall survival (OS) and disease-free survival (DFS) indicated that most of the subgroups favored the high-RMPB group. Kaplan-Meier analysis showed that overall the patients with high RPMB after R0 resection had a significantly better clinical outcome regarding DFS (hazard ratio [HR] = 0.013, p = 0.042). Additionally, high-RPMB patients, who underwent adjuvant radiotherapy with both ≥T2 tumor and positive lymph nodes, showed superior DFS in comparison with the low-RPMB group (HR = 5.35 × 10-10, n = 26, p = 0.010). RPMB might be considered as a promising biomarker for decision-making with regard to postoperative adjuvant radiotherapy for GA patients.

TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer.

The tripartite motif (TRIM) family proteins play a great role in carcinogenesis. However, the expression pattern, prognostic value and biological functions of tripartite motif containing 23 (TRIM23) in colorectal cancer (CRC) are poorly understood. Here, we found that TRIM23 is up-regulated and associated with tumour size, lymph node metastasis, American Joint Committee on Cancer (AJCC) stage and poor prognosis in CRC. Multivariate Cox regression analyses revealed that TRIM23 overexpression could be identified as an independent prognostic factor for CRC. TRIM23 could promote the proliferation of CRC cell in vitro and in vivo; additionally, TRIM23 depletion induced G1-phase arrest. Gene set enrichment analysis (GSEA) revealed that P53 and cell cycle signalling pathway-related genes were enriched in patients with high TRIM23 expression levels. We show in this study that TRIM23 physically binds to P53 and enhances the ubiquitination of P53, thereby promoting tumour proliferation. Thus, our data indicated that TRIM23 acts as an oncogene in colorectal carcinogenesis and may provide a novel therapeutic target for CRC management.

Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.

Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.

BMP Signaling in Development, Stem Cells, and Diseases of the Gastrointestinal Tract.

The bone morphogenetic protein (BMP) pathway is essential for the morphogenesis of multiple organs in the digestive system. Abnormal BMP signaling has also been associated with disease initiation and progression in the gastrointestinal (GI) tract and associated organs. Recent studies using animal models, tissue organoids, and human pluripotent stem cells have significantly expanded our understanding of the roles played by BMPs in the development and homeostasis of GI organs. It is clear that BMP signaling regulates GI function and disease progression that involve stem/progenitor cells and inflammation in a tissue-specific manner. In this review we discuss these new findings with a focus on the esophagus, stomach, and intestine.