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Introduction: The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N + M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study., Methods: Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method., Results: Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p = 0.464; Lobaplatin vs. conventional therapy group, p = 0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p = 0.020, HR = 1.927, 95% CI, 1.111-3.343; Lobaplatin: p = 0.167, HR = 0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p = 0.361, HR = 1.360, 95% CI, 0.703-2.634; Lobaplatin: p = 0.780, HR = 0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p = 0.525, HR = 1.149, 95% CI, 0.749-1.760; Lobaplatin: p = 0.117, HR = 0.488, 95% CI, 0.199-1.198)., Conclusion: Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest with respect to this manuscript., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC., Methods: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates., Results: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively., Conclusions: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.

Background: This study evaluated the safety and efficiency of intraperitoneal irrigation chemotherapy with lobaplatin for the treatment of advanced gastric cancer (GC)., Methods: A total of 56 locally advanced GC patients (experimental group) who received intraoperative intraperitoneal irrigation chemotherapy in addition to undergoing radical D2 surgery were matched 1:1 based on 8 covariates to 56 patients without drug treatment (control group). Clinical data were collected and analyzed., Result: The two groups were well balanced in basic characteristics and had comparable clinical indices. All patients had similar time to first flatus (2.8 ± 0.3 vs. 2.9 ± 0.3 d, P = 0.076), time to first oral intake (3.5 ± 3.4 vs. 4.1 ± 4.6 d, P = 0.439), and duration of postoperative hospitalization (9.1 ± 3.2 vs. 9.6 ± 4.0 d, P = 0.446). There were no significant differences in postoperative complications including anastomotic and duodenal stump leakage, abdominal and anastomotic bleeding, seroperitoneum, and incision infection between the experimental and control groups (P > 0.05). The rates of chemotherapy-related side effects including allergic reaction, neurotoxicity, diarrhea, and nausea/vomiting were also similar between the two groups, and there were no abnormalities in leukocyte and platelet levels and liver and renal function during the first 5 days after surgery., Conclusion: Intraperitoneal irrigation chemotherapy with lobaplatin is safe for patients with advanced gastric cancer.

Background: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline., Methods: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety., Results: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (P interaction  = 0.001, P interaction  = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044)., Conclusions: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future., (© 2024. The Author(s).)

Objective: To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method: Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 µmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 µmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result: Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 µmol/L (IQR: 1846.09 µmol/L). The median IC50 for lobaplatin was 85.04 µmol/L (IQR: 305.01 µmol/L).The difference between the two groups was not statistically significant ( Z =1.784, P =0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%‒47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%‒92.3%): this difference is statistically significant ( t =‒15.282, P <0.001). Conclusion: The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Background: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear., Methods: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively., Results: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002)., Conclusion: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis., (© The Author(s) 2024. Published by Oxford University Press.)

Ovarian cancer is the most lethal gynecological cancer type in the United States. The success of current chemotherapies is limited by chemoresistance and side effects. Targeted therapy is a promising future direction for cancer therapy. In the present study, the efficacy of co‑targeting IL‑6 and IL‑8 in human ovarian cancer cells by bazedoxifene (Baze) + SCH527123 (SCH) treatment was examined. ELISA, cell viability, cell proliferation, cell migration, cell invasion, western blotting and peritoneal ovarian tumor mouse model analyses were performed to analyze the expression levels of IL‑6 and IL‑8, tumor growth, tumor migration and invasion, and the possible pathways of human ovarian cancer cell lines (SKOV3, CAOV3 and OVCAR3) and patient‑derived OV75 ovarian cancer cells. Each cell line was treated by monotherapy or combination therapy. The results demonstrated that IL‑6 and IL‑8 were secreted by human ovarian cancer cell lines. Compared with the DMSO control, the combination of IL‑6/glycoprotein 130 inhibitor Baze and IL‑8 inhibitor SCH synergistically inhibited cell viability in ovarian cancer cells. Baze + SCH also inhibited cell migration and invasion, suppressed ovarian tumor growth and inhibited STAT3 and AKT phosphorylation, as well as survivin expression. Therefore, co‑targeting the IL‑6 and IL‑8 signaling pathways may be an effective approach for ovarian cancer treatment.

Background: 18 F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18 F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades., Methods: Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18 F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters., Results: A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation., Conclusions: 18 F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake., Clinical Trial Registration: NCT03036943., (© 2021. The Author(s).)

Objectives: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence., Methods: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT., Results: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging ( P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence., Conclusions: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Background: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma., Methods: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m 2 on days 1 and 22, and fluorouracil 800 mg/m 2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m 2 on days 1 and 22, and fluorouracil 800 mg/m 2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m 2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m 2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed., Findings: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; p non-inferiority =0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; p non-inferiority =0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported., Interpretation: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma., Funding: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

What Is Known and Objective: To compare short-term therapeutic efficacies and related changes of serum markers from two chemotherapeutic regimes using lobaplatin or carboplatin in combination with paclitaxel in ovarian cancer patients after cytoreductive surgery., Methods: 120 patients were recruited with pathologically confirmed ovarian cancer. Patients were equally and randomly divided into two groups receiving paclitaxel (PTX) with lobaplatin (LBP) or carboplatin (CBP, as control), respectively, 21 days as a cycle for 6 cycles. Follow-up was performed for 6 months post-treatment. The therapeutic efficacy, serum levels of CA125 (cancer antigen 125/ mucin 16) and HE4 (Human epididymis protein 4) as well as the quality of life were assessment before and after treatment., Results: No significant difference in therapeutic efficacy was observed between the groups (P > .05). The response rates at 1, 3 and 6 months were 76.7%, 66.7% and 46.7% in the LBP group and 73.3%, 63.3% and 36.7% in the CPB group, respectively. At the end of chemotherapy, serum levels of HE4 and CA125 in both groups returned to normal. However, patients in the LBP group had significantly lower HE4 and CA125 levels than those in the CPB group when examined at 3 or 6 months after chemotherapy (P < .05). Moreover, at the end of follow-up, the quality-of-life score (QLQ-C30) of the LBP group was better than that of the CBP group with statistical significance (P < .05)., What Is New and Conclusion: Both lobaplatin and carboplatin have decent anti-tumour efficacy to be involved in the standard platinum/paclitaxel-based chemotherapy against ovarian cancer. Lobaplatin, on the other hand, has demonstrated higher efficacy to control the progress of the disease yet less toxicity to warrant better patient quality of life., (© 2020 John Wiley & Sons Ltd.)

Sibutramine is a non-selective serotonin-norepinephrine reuptake inhibitor orally administered for weight loss. In a previous study, we showed pharmacological mechanisms involved in the reduction of sperm quality and fertility of rats exposed for 30 days to this anorexigen in the light phase of the light-dark (l/d) cycle. It is already known that rodents are nightlife animals, with higher metabolic activity during the dark phase than in the light phase of the light-dark (l/d) cycle. Thus, the present study aimed to investigate whether the deleterious effects on reproductive parameters after sibutramine administration would be enhanced after a shorter period of exposure during the dark phase of the l/d cycle. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/d) or vehicle for 15 days during the dark phase of the l/d cycle. Sibutramine treatment decreased final body and reproductive organ weights, as well as serum testosterone levels. Sperm transit time through the epididymis was accelerated, and sperm concentration and motility were diminished in the sibutramine-exposed rats. The decrease in sperm concentration was also verified in the epididymal histological sections. In conclusion, the deleterious effects of sibutramine on reproductive parameters of male rats were enhanced when the exposure occurred in the dark phase of the l/d cycle, even after a short exposure duration. Our results reinforce the impact of timing on drug therapeutic action., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Cisplatin is the most commonly used chemotherapeutic drug for nasopharyngeal carcinoma (NPC), while its side effects are often intolerable. Lobaplatin, as an effective third-generation platinum with fewer adverse reactions and less platinum cross-resistance, has been considered as a good alternative to cisplatin after cisplatin's failure (relapse or metastasis) in the treatment of NPC. However, the anti-NPC mechanism of lobaplatin remains largely unknown. In present study, 50% inhibiting concentration (IC50) of lobaplatin for NPC cells is found to be similar to that of cisplatin. 10 μM and 20 μM lobaplatin caused obvious gasdermin-E (GSDME)-mediated pyroptosis by activating caspase-3. Moreover, we found lobaplatin induced proteasomal degradation of cell inhibitor of apoptosis protein-1/2 (cIAP1/2). And these pyroptotic phenomena could be suppressed by the recovery of cIAP1/2, suggesting that cIAP1/2 are critical in lobaplatin-induced pyroptosis. Further inhibition of cIAP1/2 by birinapant (an antagonist of cIAP1/2) dramatically enhanced pyroptosis induced by lobaplatin in vitro and in vivo, which was consistent with the combination with cisplatin. Importantly, this synergistic pyroptotic effect were suppressed by the inhibition of Ripoptosome (RIPK1/Caspase-8/FADD), reactive oxygen species (ROS) and caspase-3 cleavage, and were independent of phosphorylation of JNK and NF-κB signal. Our data reveal that cIAP1/2 play important roles in lobaplatin-induced NPC cell pyroptosis, and this anti-NPC effect can be significantly potentiated by cIAP1/2 antagonist birinapant through regulating the formation of Ripoptosome and the generation of ROS. These study provides a possibility to further reduce the platinum-related adverse events and chemoresistance of lobaplatin while maintaining satisfactory anti-NPC efficacy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for 18 F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADC k , K), mono- (ADC m ), and biexponential functions (f, D p , D f ) while Logan plots were used to calculate volume of distribution (V T ). In total, 16 unique PET (V T , SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for V T was 0.85. T he best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and 18 F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of 18 F-FACBC PET derived parameters (V T , SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.

Background: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC)., Methods: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m intravenous lobaplatin (day 2) or 1000 mg/m intravenous gemcitabine (days 1, 8)., Results: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue., Conclusions: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC., Trial Registration: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).

Background: National Comprehensive Cancer Network guidelines consider 18 F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18 F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (<2·0 ng/mL)., Methods: This was a prospective, single-centre, open-label, single-arm comparative study done at University of California Los Angeles (Los Angeles, CA, USA). Patients older than 18 years of age with prostate cancer biochemical recurrence after radical prostatectomy and PSA levels ranging from 0·2 to 2·0 ng/mL without any prior salvage therapy and with a Karnofsky performance status of at least 50 were eligible. Patients underwent 18 F-fluciclovine (reference test) and PSMA (index test) PET-CT scans within 15 days. Detection rate of biochemical recurrence at the patient level and by anatomical region was the primary endpoint. A statistical power analysis demonstrated that a sample size of 50 patients was needed to show a 22% difference in detection rates in favour of PSMA (test for superiority). Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs one) to determine positive findings. This study is registered with ClinicalTrials.gov, number NCT02940262, and is complete., Findings: Between Feb 26, 2018, and Sept 20, 2018, 143 patients were screened for eligibility, of whom 50 patients were enrolled into the study. Median follow-up was 8 months (IQR 7-9). The primary endpoint was met; detection rates were significantly lower with 18 F-fluciclovine PET-CT (13 [26%; 95% CI 15-40] of 50) than with PSMA PET-CT (28 [56%; 41-70] of 50), with an odds ratio (OR) of 4·8 (95% CI 1·6-19·2; p=0·0026) at the patient level; in the subanalysis of the pelvic nodes region (four [8%; 2-19] with 18 F-fluciclovine vs 15 [30%; 18-45] with PSMA PET-CT; OR 12·0 [1·8-513·0], p=0·0034); and in the subanalysis of any extrapelvic lesions (none [0%; 0-6] vs eight [16%; 7-29]; OR non-estimable [95% CI non-estimable], p=0·0078)., Interpretation: With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations (≤2·0 ng/mL). Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE., Methods: Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center., Results: No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple-drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single-drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple-drug chemotherapy benefit versus single-drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller)., Conclusions: Triple-drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single-drug TACE., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: This phase II, multicenter, single arm clinical study was first performed to evaluate the therapeutic efficacy and safety of the regimen-a combination of lobaplatin (LBP) and etoposide (VP-16)-and investigate the pharmacokinetics of LBP in Chinese men older than 65 years with extensive-stage small cell lung cancer (SCLC)., Methods: Patients older than 65 were treated with the combination of LBP and VP-16 for 4-6 cycles through intravenous drip. The initial dose of VP-16 was 100 mg/m 2 /day for d1-d3 in each 21-day cycle, while LBP was administrated for d1 in each cycle based on creatinine clearance (Ccr), 20 mg/m 2 for Ccr < 60 mL/min; 25 mg/m 2 for 60 ≤ Ccr < 80 mL/min and 30 mg/m 2 for Ccr ≥ 80 mL/min. Efficacy, safety and pharmacokinetics were evaluated to confirm the therapeutic effect., Results: Thirteen elderly patients were enrolled and three patients were discontinued. The median progress-free survival was 129 days and the median overall survival was 238 days, which caused a significantly prolonged survival rate of 38.5% and a higher disease control rate of 80%. Most frequent adverse events were mild to moderate containing leukopenia, neutropenia, anemia, nausea and anorexia. Pharmacokinetic analysis revealed that there is no significant difference between LP-D1 and LP-D2 at the same dosage level. With the dosage increasing, the elimination clearance showed a slowing tendency, especially for 30 mg/m 2 group., Conclusions: LBP (20, 25, 30 mg/m 2 ) in combination with VP-16 (100 mg/m 2 ) could inhibit the elderly SCLC disease process, prolong their survival time and reduce adverse reactions via preliminary assessment and provide guidance for further investigation.

Purpose: To explore the safety and feasibility of intraoperative, intraperitoneal perfusion chemotherapy with lobaplatin for colorectal cancer (CRC)., Methods: From November 1, 2016 to January 15, 2017, a total of 100 patients with CRC in Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, who had undergone radical surgery, were randomized into two groups as follows: the lobaplatin group (50 patients) and the control group (50 patients). The time of recovery of postoperative intestinal functions, hematotoxicity, hepatic-renal toxicity, and postoperative complications were observed and analyzed, with the goal of exploring the safety and feasibility of the drug administration., Results: The time to first gas exhaust in lobaplatin and the control group was 3.08 days and 3.20 days, respectively (p=0.392). The time of defecation in lobaplatin and the control group was 4.38 days and 4.50 days, respectively (p=0.524). There was no statistically significant difference between them in terms of the time of gas exhaust and defecation. One case with intra-abdominal hemorrhage, 1 case with anastomotic leakage, 3 cases with incision complication, 1 case with adhesive intestinal obstruction, and 1 case with pulmonary infection occurred in lobaplatin group compared to 1 case with anastomotic bleeding, 1 case with anastomotic leakage, 2 cases with incision complication, 2 cases with adhesive intestinal obstruction, 2 cases with pulmonary infection, and 1 case with lymphatic fistulas occurred in control group. There was no statistically significant difference between the groups in terms of the total incidence of postoperative complications (p=0.790). No statistically significant difference was observed between the groups in terms of leukocyte and platelet levels on the first, third, and fifth postoperative day. There was also no statistically significant difference in terms of platelet level 2 weeks after surgery. Both the lobaplatin and control group had 2 cases with postoperative abnormal hepatic-renal function. A total of 6 cases in the lobaplatin group and 7 cases in the control group developed gastrointestinal reactions, showing no statistically significant difference (p=0.766)., Conclusion: Intraoperative intraperitoneal perfusion chemotherapy with lobaplatin showed no effect on short-term recovery in patients with CRC.

Background: A retrospective study was conducted to assess the efficacy and toxicity of lobaplatin-etoposide (EL) chemotherapy for small cell lung cancer (SCLC)., Methods: The clinical data of 50 patients treated in our department from May 2014 to March 2018 were obtained. Untreated patients with SCLC administered LBP intravenously (IV) at 30 mg/m 2 on day 1 and etoposide IV at 100 mg/m 2 on days 1, 2, and 3 were enrolled. The treatment was cycled every 21 days., Results: The median overall and progression-free survival rates of the 50 patients were 11.67 (range: 7.30-16.04) and 6.8 (range: 5.25-8.35) months, respectively, with an overall response rate of 66% and a disease control rate of 90%. The most frequent drug-related adverse effects were leukopenia and neutropenia, and no grade 3/4 hepatotoxicity or nephrotoxicity was observed., Conclusion: These results indicate that LBP-containing chemotherapy is effective and tolerable for SCLC in terms of response and survival., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent., Materials and Methods: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other., Results: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%)., Conclusions: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.

This study was conducted to evaluate the toxic effects and potency of 2-dodecylcyclobutanone (2-dDCB), a unique compound derived from palmitic acid via irradiation. In a series of assays of bacterial reverse-mutation, in vitro chromosomal aberration, and in vivo micronucleus, negative responses were found by the treatment of 2-dDCB comparing vehicle control, dimethyl sulfoxide or corn oil. In the acute oral toxicity test, all of the mice administrated 2-dDCB survived, and there were no clinical and necropsy signs observed at any doses (0, 300, and 2000 mg/kg body weight) during the experimental period of 14 days. These results suggested that 2-dDCB is a relatively non-toxic substance with median lethality dose higher than 2000 mg/kg body weight. Moreover, there were no adverse effects noted in rats orally administrated 2-dDCB everyday via gavage for 28 days, even at the highest dose (2.0 mg/kg body weight/day) tested, which is 1000-times higher than the human daily intake of 2-dDCB estimated through an extreme exposure scenario. Overall, these results indicate that 2-dDCB is not likely to raise any human health concerns and irradiated foods containing palmitic acid can be recognized as safe for human consumption under the current international regulation systems for food irradiation., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: The purpose of this study was to analyze the efficacy and safety of induction chemotherapy and sequential Nimotuzumab combined with concurrent chemoradiotherapy in N3M0 stage nasopharyngeal carcinoma (NPC)., Methods: This study included 45 N3 stage NPC patients treated with induction chemotherapy, sequential Nimotuzumab plus concurrent chemoradiotherapy. The intensity modulated radiation therapy (IMRT) doses for planning target volume (PTV) were 70-72 Gy for gross disease in the nasopharynx, and 66-70 Gy for positive lymph nodes. The doses for high risk and low risk regions PTV were 60-62 Gy and 54-56 Gy in 31-33 fractions. Induction chemotherapy consisted of 3 cycles of docetaxel (75 mg/m2, day 1) plus lobaplatin (30 mg/m2, day 1). Concurrent with radiotherapy, patients received chemotherapy consisting of lobaplatin 50 mg/m2, day 1. Targeted drug therapy given on the first time of IMRT consisted of Nimotuzumab (200mg, iv weekly for 7 courses). Cycle repetition of chemotherapy was every 21 days., Results: The efficacy of 3 cycles of induction chemotherapy before the start of concurrent chemoradiotherapy was 100%, and the overall efficacy after the end of chemoradiotherapy was also 100%. Three-year overall survival (OS), distant metastasis-free survival (DMFS), locoregional control (LRC) and progression-free survival (PFS) rates were 85.6, 81.9, 97.8 and 79.5%, respectively. The main adverse reactions were hematologic toxicity, particularly neutropenia (100%), anemia (88.9%) and thrombocytopenia (68.9%). Patients developed a relatively low degree of mucositis and vasculitis. Chronic toxicity was mainly grade I-II radiation-induced xerostomia (18 cases). There were 11 cases of hearing loss and 4 cases of neck skin fibrosis. No cases of treatment-related death and radiation-induced cranial nerve damage or trismus were observed., Conclusion: In N3 stage NPC, induction chemotherapy and sequential Nimotuzumab plus concurrent chemoradiotherapy yielded an excellent survival benefit, and the toxicities were tolerable. Distant metastasis was the main cause of treatment failure.

Objective: To investigate the efficacy and safety of lobaplatin (LBP) plus S-1 for advanced gastric cancer (AGC) and determine the potential role of circulating tumor cells (CTC) for predicting the therapeutic response and prognosis. Methods: From January 2014 to February 2015, 64 consecutive patients with AGC received lobaplatin plus S-1 chemotherapy in Liaocheng People's Hospital. The clinical features, clinical response, adverse effects, prognosis and CTC pre- and post-treatment were retrospectively analyzed. The correlation between CTC and patients' disease control rate (DCR), objective response rate (ORR), progression free survival (PFS) as well as overall survival (OS) were investigated. Results: All 64 patients completed 2 cycles of chemotherapy.The number of patients who achieved complete regression, partial regression, stable and progression were 0, 24 (37.5%), 18 (28.1%) and 22 (34.4%), respectively. ORR was 37.5% and DCR was 65.6%. The median PFS was 10.8 months(95% CI 7.1-12.0) and the median OS was 16.1 months(95% CI 12.4-18.8). The ORR and PFS were not significantly different between patients with baseline CTC≥2 and CTC<2 (25.0% vs 53.6%, P =0.150; 6.2 months vs 7.5 months, P =0.780), while the DCR and OS were significantly different (45.9% vs 90.0%, P =0.008; 10.5 months vs 17.2 months, P <0.001). After 2 cycles of chemotherapy, the ORR and DCR in patients with CTC≥2 were 16.7% and 45.9%, respectively, which were significantly lower than those observed in patients with CTC<2 (50.0% and 90.0%, respectively). The former also had shorter median PFS and OS (6.6 months vs 8.9 months, 8.4 months vs 15.0 months, respectively). Patients with persistently CTC<2 or those exhibiting an conversion to CTC<2 following chemotherapy had an improved PFS and OS, while patients with persistently CTC≥2 or those exhibiting an conversion to CTC≥2 following therapy had shorter PFS and OS.The most frequent adverse effects were grade 1 or 2 gastrointestinal discomfort and myelosuppression. No patients discontinued chemotherapy because of adverse events. Conclusions: Lobaplatin plus S-1 had manageable safety profile and promising antitumor activity in patients with AGC. CTC could be used as a biomarker in evaluating therapeutic response and predicting their prognosis.

To observe and analyze the therapeutic effect of combinated application of lobaplatin and irinotecan in treating recurrant small cell lung cancer. The 140 patients who were treated in our hospital for recurrant small cell lung cancer were selected as research objects. All selected patients were subjected to combined application of obaplatin and irinotecan, the total therapeutic effect was observed, and the adverse reactions occurring during treatment were recorded. Through observing the total treatment effective ratio of 140 patients recurrant small cell lung cancer, the number of complete remission cases, number of partial remission cases, number of stable disease cases, and number of disease progression cases were 40(28.57%), 28(20.00%), 30(21.43%), 42(30.00%), respectively, with total effective ratio of 48.57%. The average time to progression (TTP) was (4.5±0.8) months, average overall survival (OS) was (7.6±1.2) months. The toxic and adverse effects mainly included hematological toxicity and gastrointestinal adverse reaction, such as leukocyte reduction, neutrophil reduction, thrombocytopenia, decreased hemoglobin, nausea and vomiting, diarrhea. No toxicity-related death occurred. In treatment of patients with recurrant small cell lung cancer, the combined application of lobaplatin and irinotecan can achieve great results, which is a safe and reliable way of treatment.

Background: Malignant pleural effusion is a common complication of non-small cell lung cancer (NSCLC); however, treatment options remain limited. This study evaluated the safety and efficacy of sequential intrapleural therapy with lobaplatin and erythromycin for NSCLC-mediated malignant pleural effusion., Methods: Fifty-six patients with NSCLC complicated with malignant pleural effusion were recruited for a prospective single-arm study from December 2014 to 2016; one patient dropped out. In addition to conventional systemic chemotherapy, lobaplatin and erythromycin were intrapleurally injected into subjects. Short and long-term responses were analyzed. The concentration of ultrafilterable platinum in the pleural effusion and plasma were detected at different time points. Incidences of severe adverse reactions were observed., Results: In the 55 evaluable patients, the effective rate of pleural effusion was 81.8% after six weeks of treatment. Six and twelve months after treatment, the effective rates were 60% and 21.8%, respectively, and the one-year survival rate was 83.6%. The concentrations of lobaplatin in pleural effusion and plasma two hours after injecting 50 mg lobaplatin into the thoracic cavity were 13.763 ± 1.523 μg/mL and 1.120 ± 0.164 μg/mL, and 17 hours later were 1.961 ± 0.351 μg/mL and 0.578 ± 0.095 μg/mL, respectively. The rate of severe adverse reactions of the first cycle of systemic chemotherapy combined with lobaplatin and erythromycin did not significantly differ from the rate in the second cycle., Conclusion: Intrapleural combination therapy with lobaplatin and erythromycin is a safe and efficient treatment for patients with NSCLC-mediated malignant pleural effusion., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors are described. Compound 19 showed high inhibitory potency at SGLT1 (IC 50  = 45 nM), and excellent potency at SGLT2 (IC 50  = 1 nM). It also displayed excellent PK profiles in mice, rats, dogs and monkeys (F = 78-107%). In SD rats, compound 19 treatments significantly reduced blood glucose levels in a dose-dependent manner. In ZDF rats, compound 19 displayed anti-hyperglycemic effect up to 24 h. Therefore, compound 19 may serve as valuable pharmacological tool, and potential use as a treatment for metabolic syndrome., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Currently, one sixth of triple-negative breast cancer (TNBC) patients who receive docetaxel (T) and epirubicin (E) as neoadjuvant chemotherapy achieve a pathologic complete response (pCR). This study evaluates the impact of adding lobaplatin (L) to the TE regimen. Here, we show data from 125 patients (63 TE and 62 TEL patients). Four patients did not complete all the cycles. Two-sided P values show that the addition of L (38.7% vs. 12.7%, P = 0.001) significantly increases the rate of pCR in the breast and the axilla (TpCR) and the overall response rate (ORR; 93.5% vs. 73.0%, P = 0.003). The occurrence of grade 3-4 anemia and thrombocytopenia is higher in the TEL group (52.5% vs. 10.0% and 34.4% vs. 1.7% respectively). These results demonstrate that the addition of L to the TE regimen as neoadjuvant chemotherapy improves the TpCR and the ORR rates of TNBC but with increased side effects.

Objective: To explore the mechanism by which lobaplatin, as monotherapy and in combination with paclitaxel, inhibits the proliferation of human gastric cancer SGC-7901 cells., Methods: After treatment, the MTT assay was used to assess cell viability; cell cycle distribution was evaluated flow-cytometrically. Western blot was used to quantitate cyclin D1, E1, B1, and Cdk2/4 protein levels., Results: Lobaplatin and paclitaxel inhibited SGC-7901 cell growth in a concentration and timedependent manner, with IC25 values at 48h of 1.97±0.17µg/ml and 1.98±0.19 ng/ml, respectively. Interestingly, both drugs synergistically inhibited SGC-7901 cells (combination index [CI]<0.95). Lobaplatin did not affect cyclin D1 and CDK4 protein expression, while cyclin E1 and CDK2 levels were significantly increased, with cyclin B1 amounts markedly decreased (p<0.05). More S phase cells were observed after lobaplatin treatment compared with controls (60.03±1.25 vs. 18.69±0.96%; p<0.05). After treatment with paclitaxel, cyclin D1 and CDK4 protein levels were similar to control values; meanwhile, cylinE1 and CDK2 protein amounts were reduced, with increased cyclin B1 levels, compared with control values (p<0.05). More G2/M cells were obtained after treatment with paclitaxel compared with control values (74.54±0.92 vs. 18.62±0.44% (p<0.05). Lobaplatin and paclitaxel combination did not affect cyclin D1 and CDK4 protein levels (p>0.05); meanwhile, cyclin E1 and CDK2 levels were increased, with reduced cyclin B1 amounts, compared with control values (p<0.05). Notably, more S (43.23±0.81 vs. 22.32±0.86%) and G2/M (31.22±0.96 vs. 25.81±2.08%) phase cells were obtained after combined treatment compared with control values., Conclusion: Lobaplatin and paclitaxel synergistically inhibit SGC-7901 cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Aims: Weight loss is expected to improve glycaemic control in patients with diabetes or at high risk hereof. Sibutramine causes weight loss and is associated with an increased risk of myocardial infarction and stroke in high-risk patients. We examined the impact of sibutramine-induced weight loss on glycaemic control., Methods and Results: In total, 8192 obese patients with diabetes were randomized to sibutramine or placebo plus diet and exercise after a preliminary 6 weeks in which all patients received sibutramine. Patients were classified into four groups of weight change. A total of 1582 patients had a weight loss >5.7 kg; 2047 patients lost 3.7-5.7 kg; 2432 patients lost <3.7 kg, and 1875 patients gained weight. Patients on sibutramine lost slightly more weight than those on placebo (-0.2 kg on average, P < 0.0001). Mean blood glucose changes in the placebo group were -0.6 mmol/L (±3.1, P = 0.0002), -0.2  mmol/L (±2.7, P = 0.04), and -0.1  mmol/L (±3.0, P = 0.01) in the moderate, modest, and mild weight loss groups, respectively; in the weight gain group blood glucose levels increased by +0.2 mmol/L (±3.1, P = 0.003). Corresponding mean blood glucose changes in the sibutramine-treated patients were -0.4 mmol/L (±3.2, P = 0.0002), +0.1 mmol/L (±3.0, P = 0.04), +0.4 mmol/L (±2.8, P = 0.01), and +0.2 mmol/L (±3.4, P = 0.003). Mean values of HbA1c followed the same pattern though the HbA1c changes were smaller with weight loss and greater with weight gain in the sibutramine group. All results were statistically significant (P < 0.0001)., Conclusion: Weight loss induced by sibutramine, diet, and exercise attenuates falls in blood glucose levels and HbA1c compared with similar weight loss with placebo, diet, and exercise., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Background: Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward malignant cells. The dye selected for our study, symmetrical diiodinated squaraine, is one of the newly developed photosensitizers. The study is designed to determine the efficacy of PDT mediated by symmetrical diiodinated squaraine in skin tumor induced Swiss albino mice., Methods: Skin tumor was induced in mice with dimethyl benzanthracene (DMBA) and croton oil. After squaraine administration to the tumor mice, photodynamic treatment of tumors was performed using a 1000W halogen lamp corresponding to the light dose of 100J/cm 2 . The mice were euthanized and skin flaps and tumor tissues from the back of mice were excised for biochemical studies. The biochemical parameters analyzed include some relevant tumor markers for epithelial tissues, inflammatory markers and markers of apoptosis. The gene expression studies were done by RT-PCR., Results: After two weeks of the treatment, there was significant inflammation. However at 90days after PDT, the parameters reverted to near-normal values. All marker parameters of tumor progression brought back to normal levels by PDT. Increased caspase-3 activity in PDT treated group shows that cell death might have occurred by apoptosis. The gene expression profile confirms the results., Conclusions: The results of the whole study show the therapeutic efficacy and apoptosis mediated tumor destruction by squaraine PDT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

18 F-Fluciclovine ( trans -1-amino-3- 18 F-fluorocyclobutanecarboxylic acid; anti - 18 F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14 C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3 H-2-deoxy-2-fluoro-D-glucose ( 3 H-FDG), 3 H-choline chloride ( 3 H-choline), and 99m Tc-hydroxymethylene diphosphonate ( 99m Tc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14 C-fluciclovine, 3 H-FDG, and 3 H-choline, but not 99m Tc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99m Tc-HMDP accumulated mostly in osteoblastic lesions. 14 C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14 C-fluciclovine and 3 H-FDG existed, based on histological differences: low 14 C-fluciclovine and high 3 H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14 C-fluciclovine was not clear, yet clearer than with 3 H-FDG. Although half of the osteoblastic lesions with 14 C-fluciclovine accumulation showed negligible 3 H-choline accumulation in comparison, they were histologically similar to lesions with marked 14 C-fluciclovine and 3 H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions., Competing Interests: Conflict of interest: Shuntaro Oka, Masaru Kanagawa, Yoshihiro Doi, and Hirokatsu Yoshimura are employees of Nihon Medi-Physics (Tokyo, Japan). We are collaborating with Mark M. Goodman and David M. Schuster for nonclinical and clinical studies on 18F-fluciclovine. Mark M. Goodman and Emory University are eligible to receive royalties from Nihon Medi-Physics. David M. Schuster is receiving research support through Emory University from Nihon Medi-Physics and Blue Earth Diagnostics (Oxford, United Kingdom). There is no other potential conflict of interest relevant to this article to declare.

Purpose: [ 18 F]Fluciclovine PET imaging shows promise for the assessment of prostate cancer. The purpose of this PET/MRI study is to optimise the PET imaging protocol for detection and characterisation of primary prostate cancer, by quantitative evaluation of the dynamic uptake of [ 18 F]Fluciclovine in cancerous and benign tissue., Methods: Patients diagnosed with high-risk primary prostate cancer underwent an integrated [ 18 F]Fluciclovine PET/MRI exam before robot-assisted radical prostatectomy with extended pelvic lymph node dissection. Volumes-of-interest (VOIs) of selected organs (prostate, bladder, blood pool) and sub-glandular prostate structures (tumour, benign prostatic hyperplasia (BPH), inflammation, healthy tissue) were delineated on T2-weighted MR images, using whole-mount histology samples as a reference. Three candidate windows for optimal PET imaging were identified based on the dynamic curves of the mean and maximum standardised uptake value (SUV mean and SUV max , respectively). The statistical significance of differences in SUV between VOIs were analysed using Wilcoxon rank sum tests (p<0.05, adjusted for multiple testing)., Results: Twenty-eight (28) patients [median (range) age: 66 (55-72) years] were included. An early (W1: 5-10 minutes post-injection) and two late candidate windows (W2: 18-23; W3: 33-38 minutes post-injection) were selected. Late compared with early imaging was better able to distinguish between malignant and benign tissue [W3, SUV mean : tumour vs. BPH 2.5 vs. 2.0 (p<0.001), tumour vs. inflammation 2.5 vs. 1.7 (p<0.001), tumour vs. healthy tissue 2.5 vs. 2.0 (p<0.001); W1, SUV mean : tumour vs. BPH 3.1 vs. 3.1 (p=0.771), tumour vs inflammation 3.1 vs. 2.2 (p=0.021), tumour vs. healthy tissue 3.1 vs. 2.5 (p<0.001)] as well as between high-grade and low/intermediate-grade tumours (W3, SUV mean : 2.6 vs. 2.1 (p=0.040); W1, SUV mean : 3.1 vs. 2.8 (p=0.173)). These differences were relevant to the peripheral zone, but not the central gland., Conclusion: Late-window [ 18 F]Fluciclovine PET imaging shows promise for distinguishing between prostate tumours and benign tissue and for assessment of tumour aggressiveness.

To retrospectively analyze the safety and efficacy of 350-560 μm gelatin sponge particles combined with single-chemotherapy drug transcatheter arterial chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma without surgical resection.Thirty elderly hepatocellular carcinoma patients without surgical resection, who received Gs-TACE in our hospital, were selected. Slowly injected gelatin sponge particles (350-560 μm)+ 10 mg lobaplatin injection into the regional embolization tumor target vessel. The Response Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response after intervention surgery.Eighty-nine times of intervention TACE were conducted on the 30 patients. The average size of tumor was 8.3 cm. The median survival time was 28 months, and the 1 and 2-year survival rates were 89% and 58%, respectively. The Response Evaluation Criteria for Solid Tumors was used to evaluate the tumor response, and found that the complete response, partial response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after intervention surgery. The patients were divided into groups: 60 to 65 years age group (A), >65 to 75 years age group (B), and >75 years age group (C); the median survival times were 16, 32, and 33 months, respectively, and there was statistical difference between A group, B group, and C group. The analysis of prognosis factors showed that there was statistical significance in age, Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal protein (AFP), and age was the protective factor.Gelatin sponge particles (350-560 μm), combined with transcatheter arterial chemoembolization, provide an alternative method for the treatment of elderly hepatocellular carcinoma without surgical resection.

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant K d of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo K d . This method was applied in a study of healthy human subjects with the histamine H 3 receptor radioligand [ 11 C]GSK189254 to measure the PK-occupancy relationship of the H 3 antagonist PF-03654746. From three test/retest studies, [ 11 C]GSK189254 K d was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%-97% and 30%-93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%-15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H 3 binding sites ( RO max  = 100%), and its IC 50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC 50 was 26% higher.

Background: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined., Methods: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates., Results: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively., Conclusion: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted., Trial Registration: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31 st , 2012, number ChiCTR-ONC-12002060 .

Purpose: We evaluated the clinical efficacy of gelatin sponge microparticle (GSM) -mediated chemoembolization for the treatment of patients with liver metastases following surgery for gastrointestinal tumors., Materials and Methods: In a retrospective analysis of 37 patients who were treated at our hospital with GSM-mediated chemoembolization for liver metastases over 13 years, we evaluated outcomes using a modified response evaluation criteria in solid tumors system and also assessed liver function and adverse effects. All patients had previously undergone surgery for gastrointestinal tumors., Results: Treatment produced various degrees of necrosis and shrinkage of lesions among our patients. Two patients achieved a complete response (CR), 27 showed a partial response (PR), five had stable disease, and three had progressive disease. The overall response rate (CR + PR) was 78%, and no severe adverse effects were observed., Conclusion: GSM-mediated chemoembolization showed good clinical efficacy in the treatment of liver metastases after gastrointestinal tumor surgery. However, larger cohort and clinical controlled studies are warranted.

Introduction: Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker., Methods: Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment., Results: Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention., Conclusion: Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Background: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers., Methods: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed., Results: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE., Conclusions: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC., Trial Registration: ClinicalTrials.gov, NCT00454519.

To evaluate the efficacy and safety of the chemotherapy program of docetaxel combined with lobaplatin for Chinese patients with pulmonary and hepatic metastasis of nasopharyngeal carcinoma (NPC). This study included 37 NPC patients with pulmonary and hepatic metastasis. The chemotherapy program included docetaxel (75 mg/m, day 1) plus lobaplatin (30 mg/m, day 1). Cycle repetition was every 21 days. Patients were monitored for 7-41 months, with a median follow-up duration of 18 months. The total efficiency of this group was 67.6% and the disease control rate was 81.1%. The median progression-free survival was 9.4 months (95% confidence interval, 6.8-14.3 months), the median overall survival was 18.3 months (95% confidence interval, 13.7-22.8 months), and the 2-year survival rate was 37.8%. The main hematological toxicities were leukopenia (91.9%), anemia (81.1%), and thrombocytopenia (70.3%); other adverse reactions were mild. Changes in Epstein-Barr-DNA levels can basically reflect the dynamic changes in the efficacy of chemotherapy. Docetaxel combined with lobaplatin has a favorable outcome for the treatment of pulmonary and hepatic metastatic NPC. It has been a convenient regimen with tolerable toxicity.

Background: This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat peritoneal carcinomatosis (PC) from gastric cancer (GC)., Methods: A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at (43 ± 0.5) °C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles., Results: At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC) 0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy ≥6 cycles, and peritoneal cancer index ≤20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy ≥6 cycles as the independent predictor for better survival., Conclusions: CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA., (Copyright © 2016 Elsevier B.V. All rights reserved.)