Inhibition of the thioredoxin system for radiosensitization therapy of cancer.

Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt3)]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy. In this review, the sensitization mechanisms and the current research progress of these radiosensitizers are discussed in detail, with the overall aim of providing valuable insights for the judicious application of Trx system inhibitors in the field of cancer radiosensitization therapy.

Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma: a case report.

BACKGROUND: Perianal Paget's disease (PPD) is a rare malignancy, often associated with an underlying adenocarcinoma and a poor prognosis. CASE PRESENTATION: A 69-year-old female was presented with a history of perianal pruritus for 6 months and enlarged inguinal lymph nodes in the left side. Paget cells were confirmed by pathology after a wide excision of perianal skin. Radiotherapy was performed covering the bilateral inguinal lymphatic drainage area. Hepatic metastasis was found 8 months after surgery. Hepatic artery embolization (HAE) and high-intensity focused ultrasound therapy (HIFU) were performed successively. However, hepatic metastasis happened again 3 months later. Ultrasound-guided percutaneous radiofrequency ablation (PRFA) was carried out and various means of inspection could not identify the primary tumor. In the case of rapid progression of the tumor, we gave the patient chemotherapy regimens of XELOX. After 4 cycles of chemotherapy, the tumor marker went down continuously and the hepatic metastasis stayed stable. CONCLUSIONS: Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma may benefit from XELOX on the basis of adenocarcinoma.

Colon metastasis from hepatocellular carcinoma: a case report and literature review.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with frequent intrahepatic metastases; extrahepatic metastases are not rare but less frequent compared to intrahepatic ones. The most frequent sites of extrahepatic metastases are the lungs, followed by the lymph nodes, bones, and adrenal glands. Case report covering gastrointestinal (GI) tract involvement from HCC is limited. CASE PRESENTATION: A 60-year-old man was referred to us in May 2019 with a diagnosis of sigmoid colon tumor. The patient had a history of HCC and had received two stages of open resections for the primary and the abdominal metastasis successively and many times of transcatheter arterial chemoembolization (TACE). The sigmoid colon tumor received Hartmann procedure after abdominal enhanced computerized tomography (CT) scan and colonoscopy, while postoperative pathology and immunohistochemistry identified it as extrahepatic colonic metastasis from HCC. CONCLUSIONS: The ratio of extrahepatic metastasis to the digestive tract was very low, and the majority was upper gastrointestinal involvement because of direct invasion or intraperitoneal implantation. TACE may be the risk factor of retrograde hematogenous metastasis to the downstream colon.

Preoperative C-reactive protein-to-albumin ratio predicts anastomotic leak in elderly patients after curative colorectal surgery.

BACKGROUND: Anastomotic leak (AL), as one of the most devastating complications, is the leading cause of mortality in colorectal cancer (CRC) patients after resection. This study was aimed to investigate potential risk factors for AL in elderly surgical CRC patients. METHODS: A total of 1068 elderly subjects who underwent elective curative colorectal surgery from 2012 to 2018 were retrospectively evaluated and enrolled into this study population. The predictive value of C-reactive protein-to-albumin ratio (CAR) for AL in surgical CRC patients was evaluated by receiver operating characteristic (ROC) curve analysis. Potential risk factors for AL were assessed by the univariate and multivariate logistic regression analyses. RESULTS: Of all the 1068 enrolled patients, 81 patients have developed AL with an incidence of 7.6% (81/1068). Preoperative CAR was an effective predictor for AL with an area under the curve (AUC) of 0.758, 95% CI of 0.700-0.817, a cut-off value of 2.44, a sensitivity of 61.09% and a specificity of 80.25%, respectively (P< 0.001). Duration of operation (OR: 2.05, 95% CI: 1.21-3.44, P= 0.013) and preoperative CAR (OR: 1.94, 95% CI: 1.21-3.11, P= 0.007) were two independent risk factors for AL by the multivariate logistic regression analysis. CONCLUSIONS: Our study indicate that preoperative CAR level and duration of operation were two independent predictors for AL among elderly surgical CRC patients.

The long noncoding RNA TPTE2P1 promotes the viability of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) have important functions in tumor development and progression, including colorectal cancer (CRC), but their roles are not completely understood. In this study, the roles of the lncRNA transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1), previously implicated in gallbladder cancer cell migration and invasion, were evaluated in CRC. In particular, quantitative polymerase chain reaction was used to quantify TPTE2P1 levels in tumor tissues and cell lines. The association between TPTE2P1 and survival was analyzed using the online tool OncoLnc. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, colony formation assays, and flow cytometry were used to evaluate the effects of TPTE2P1 on viability, cell cycle progression, and apoptosis. Signaling pathway proteins were quantitated by Western blot analysis. Finally, the role of TPTE2P1 was analyzed in vivo using mouse models. TPTE2P1 levels were significantly higher in CRC tissues than in adjacent normal tissues. Higher expression was associated with a poor survival rate. The silencing of TPTE2P1 led to cell cycle arrest at the S phase and thereby inhibited cell viability. TPTE2P1 knockdown also caused cancer cell apoptosis via the activation of the apoptosis regulator (BCL2)/caspase 3 signaling cascade. In addition, the inhibition of TPTE2P1 had suppressive effects on tumors in vivo. TPTE2P1 is upregulated in CRC and plays essential roles in the regulation of cell viability in vitro and tumor formation in vivo.

Pyoderma gangrenosum around an ileostoma: A case report.

RATIONALE: Pyoderma gangrenosum (PG) is a rare postoperative complication of enterostomy, mostly developing from dermatitis, which may have serious consequence. PATIENT CONCERNS: A patient with lower rectal cancer receiving low anterior resection (LAR) and protective ileostomy was initially diagnosed with dermatitis, which very quickly developed to PG, though no medical or familial history was found. DIAGNOSIS: We diagnosed the patient with peristoaml dermatitis starting from a tiny skin ulceration, but corrected the diagnosis to PG because of the rapid development and severe consequences. INTERVENTIONS: Routine stoma care did not improve the condition, so we performed 2 terms of debridement, the closure of the stoma and autologous skin transplantation before finally solving the problem. OUTCOMES: The patient was discharged 60 days after the first surgery and 5 days after the last one. After 18 months of follow-up, the patient kept in a stable condition. LESSONS: Medical staff should not neglect peristoaml dermatitis because of its common occurrence. Once the situation develops beyond the doctors' expectation, more efforts should be made to treat it, even expand debridement if possible.

Knockdown of TCTN1 Strongly Decreases Growth of Human Colon Cancer Cells.

BACKGROUND Tectonic family member 1 (TCTN1), a member of the tectonic family, is involved in several developmental processes and is aberrantly expressed in multiple solid tumors. However, the expression and regulation of TCTN1 in human colorectal cancer (CRC) is still not clear. MATERIAL AND METHODS The expression of TCTN1 mRNA was first explored by using Oncomine microarray datasets. TCTN1 expression was silenced in human CRC cell lines HCT116 and SW1116 via RNA interference (RNAi). Furthermore, we investigated the effect of TCTN1 depletion on CRC cell growth by MTT, colony formation, and flow cytometry in vitro. RESULTS In this study, meta-analysis showed that the expressions of TCTN1 mRNA in CRC specimens were significantly higher than that in normal specimens. Knockdown of TCTN1 expression potently inhibited the abilities of cell proliferation and colony formation as determined. Flow cytometry analysis showed that depletion of TCTN1 could cause cell cycle arrest at the G2/M phase. In addition, Annexin V/7-AAD double-staining indicated that TCTN1 silencing promoted cell apoptosis through down-regulation of caspase 3 and Bcl-2 and upregulation of cleaved caspase 3 and PARP. CONCLUSIONS Our results indicate that TCTN1 may be crucial for CRC cell growth, providing a novel alternative to target therapies of CRC. Further research on this topic is warranted.

Mechanisms of electroacupuncture effects on acute cerebral ischemia/reperfusion injury: possible association with upregulation of transforming growth factor beta 1.

Electroacupuncture at the head acupoints Baihui (GV20) and Shuigou (GV26) improves recovery of neurological function following ischemic cerebrovascular events, but its mechanism remains incompletely understood. We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1 (TGF-ß1). To test this, we established a rat model of cerebral ischemia by middle cerebral artery occlusion. Electroacupuncture was performed at Baihui and Shuigou with a "disperse-dense" wave at an alternating frequency of 2 and 150 Hz, and at a constant intensity of 3 mA. Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days. Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment. Furthermore, serum level of TGF-ß1 was greater after electroacupuncture than after no treatment. Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-ß1 in rats with acute cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

Influence of dual-task on postexercise facilitation: a transcranial magnetic stimulation study.

In this study we investigated the effect of a dual task (DT) comprised of a nonfatiguing leg and foot extension coupled with a calculation task on postexercise facilitation (PEF) of motor evoked potentials (MEPs) tested by using transcranial magnetic stimulation (TMS). Twelve right-handed healthy subjects participated in the study. They were required to perform a motor task, a cognitive task and a DT. The motor task consisted of extending the right leg and foot for 30 sec at 20% of the maximal voluntary contraction. The cognitive task consisted of a 30-sec backward calculation. In the DT condition, motor and cognitive tasks were performed concurrently. Resting motor threshold and 10 MEPs were collected before and immediately after each task. TMS was delivered to the motor hot spot of the right vastus lateralis and tibialis anterior (TA) muscles. Results showed that exercise induced a significant PEF in both VL and TA muscles while calculation was not associated with significant PEF. Furthermore, DT was associated with lack of significant PEF in both muscles (VL, 116.1%±9.6%; TA, 115.7%±9%). Our data indicates DT interference on corticospinal excitability after a nonfatiguing exercise. Our experimental paradigm may be used to address postexercise motor cortex plastic adaptations induced by motor and cognitive tasks of different complexity in sport, aging and neuropsychiatric diseases.

Symmetric corticospinal excitability and representation of vastus lateralis muscle in right-handed healthy subjects.

The purpose of this study was to determine the size and location of the representations of the anterior thigh muscles on the human motor cortex in the dominant and non-dominant hemispheres. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation were recorded from the right and left vastus lateralis (rVL, lVL) muscles. A total of ten right-handed healthy volunteers participated in the study. In a single session experiment, we investigated VL muscle corticospinal excitability (motor threshold, MEP size, short interval intracortical inhibition, intracortical facilitation) and cortical representation (map area, volume, and location) in the dominant and non-dominant hemispheres. The motor threshold, MEPs, and intracortical excitability did not differ significantly between the hemispheres (P > 0.05). Furthermore, no difference between sides was found in the location of VL motor representation (mediolateral and anteroposterior axis) or in map area and volume (P > 0.05). Vastus lateralis muscle corticospinal excitability and cortical map were symmetrical in right-handed subjects. Future studies on patients with unilateral lower extremity injuries could examine side-to-side plastic reorganization in corticomotor output and map location in both hemispheres.