PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer.

Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.

Clinical application of V-shaped folded submental flap in the repair of oral defect. / Våž‹æŠ˜å é¢ä¸‹çš®ç“£ä¿®å¤å£è ”ç¼ºæŸçš„ä¸´åºŠåº”ç”¨.

OBJECTIVES: The repair of small and medium-sized defects in the oral has always been a challenge, free skin flap and distal pedicled tissue flaps are difficult to meet clinical needs, and the traditional under-chin flap has the risk of donor-area injury. This study aims to investigate the efficacy of V-shaped folded submental flap in the repair of small-sized and medium-sized oral defects. METHODS: The clinical data of 28 patients with oral defect lesions, who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to December 2022, were retrospectively analyzed. Patients were divided into a V-shaped folded group (17 cases) and a conventional group (11 cases) according to different surgical methods. The V-shaped folded group was treated with a V-shaped folded submental flap for postoperative soft tissue repair, while the conventional group was treated with a conventional submental flap for repair. The postoperative follow-up time was 6-48 months. The survival status, repair time, and repair effect of the 2 groups were compared. RESULTS: There was no significant difference in flap survival rate, flap size, flap preparation time, repair surgery time, and postoperative hospital stay between the 2 groups (all P>0.05). At 6 months after the surgery, the V-shaped folded group had no difficulty in raising the head or everting the lower lip, no "cat ear" deformity in the submental skin. Scars in the V-shaped folding group were hidden at the lower edge of the mandible. The wound aesthetics and functional scores in the V-shaped folded group were significantly higher than those in the conventional group (both P<0.05). CONCLUSIONS: The V-shaped foldable submental flap has the advantages of flexible design, simple preparation, reliable blood supply, and protection of the donor area, which can effectively protect the appearance of the chin and avoid functional disorders.

Hypoxanthine guanine phosphoribosyltransferase 1, a target of miR-125b-5p, promotes cell proliferation and invasion in head and neck squamous cell carcinoma.

The mechanism of hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) upregulation and its function in head and neck squamous cell carcinoma (HNSCC) remains obscure. Herein, the expression and function of HPRT1 and the mechanism underlying its upregulation in HNSCC were explored. Firstly, the expression of HPRT1 and its prognostic values were simultaneously validated using bioinformatic analysis and quantitative real-time PCR (qRT-PCR), and immunohistochemistry staining with local HNSCC samples. The effects of HPRT1 knockdown on proliferation and invasion of HNSCC cells were detected using cell counting kit-8 (CCK-8), plate clone formation, Transwell invasion, nude mouse xenograft model assays. Moreover, the miRNA targeting HPRT1 was validated using dual-luciferase report assay, qRT-PCR and Western blot analysis. The functions of miRNA targeting HPRT1 and its dependence on HPRT1 were further investigated in HNSCC. The results indicated that HPRT1 was highly expressed in HNSCC tissues and cells, which positively correlated with advanced tumor progression and predicted poor prognosis in patients with HNSCC. HPRT1 knockdown markedly inhibited proliferation and invasion of HNSCC cells both in vitro and in vivo. MiR-125b-5p, which was downregulated and positively correlated with a favorable outcome for patients, directly targeted and downregulated HPRT1 expression, and subsequently suppressed cell proliferation and invasion in HNSCC. Collectively, the present study demonstrates that HPRT1 upregulation, at least partially caused by miR-125b-5p downregulation, could promote the malignant progression of HNSCC, highlighting the potential application of the miR-125b-5p/HPRT1 axis as a novel indicator and target in the diagnosis and treatment of HNSCC.

Clinical application of double V-Y advancement mucosal flap to repair tongue defect. / 双V-Y推进黏膜瓣修复舌部缺损的临床应用.

OBJECTIVES: The repair of small- and medium-sized defects in the oral tongue has always been a challenge, and the effect of free flap and distal pedicle flap is still far from satisfactory. Tongue flap is an ideal choice for repairing small- and medium-sized defects. However, the disadvantages such as poor local morphology restricts the development of this operation.This study aims to investigate the efficacy of double V-Y advancement mucosal flap in repair of small- and medium-sized defects of the tongue defect. METHODS: The clinical data of 15 patients with tongue defect lesions who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to May 2022 were retrospectively analyzed. After the lesions were completely excised, the mucosa and part of the tongue defect were left. One V-Y advancement mucosal flap was designed anteriorly and posteriorly to the defect. The superficial mucosa was incised gradually all around, preserving the deep median muscle tip. The 2 flaps were freed toward the middle of the defect, and the anterior and posterior flaps were sutured together at the middle of the defect, with the donor area directly pulled together and sutured. RESULTS: The double V-Y advancement mucosal flap survived in 15 patients, and the wounds healed at stage I. The postoperative follow-up time was 12-22 months, and the patients had no recurrence, with symmetrical tongue shape, and no traction and deformation in the affected tongue organs. Meanwhile, the intraoral flap was thin and flat, and healed well with the surrounding mucosa, without obvious flap contracture or tongue bite. CONCLUSIONS: Double V-Y advancement mucosal flap has the advantages of flexible design, simple preparation, reliable blood supply, and good protection of the donor site, which may be one of the effective methods for repairing small- and medium-sized defects in the anterior tongue mucosa.

V-shaped Folded Nasolabial Flap in the Repair of the Anterior Buccal Mucosal Defect.

OBJECTIVE: To investigate the efficacy of V-shaped folded nasolabial flap in the repair of small-sized and medium-sized defects of the anterior buccal mucosa. METHODS: From March 2019 to December 2021, 9 cases of male patients with anterior buccal mucosal lesions were enrolled in this study. After the lesions were completely excised, the mucosa and part of the buccal mucosal defect were left. A transverse V-shaped folded nasolabial flap was created with the pedicle located at the corner of the mouth and the long axis along the nasolabial fold. The lower part was lifted from the end to the pedicle. Next, from the level of the superficial musculo-aponeurotic system, the upper and lower parts were lifted from the end to the pedicle, and the V-shaped flap was folded and turned over through the buccal tunnel to repair the mucosal defect. The extraoral donor site was directly pulled and sutured. RESULTS: The nasolabial flap survived in 9 patients, and the wounds inside and outside the mouth healed at stage I. The postoperative follow-up time was 4 to 32 months, and the patients had no recurrence, with symmetrical buccal shape, and no traction and deformation in the affected buccal organs. In addition, the linear scar had no obvious hyperplasia and was hidden in the affected nasolabial folds, without symptoms of buccal nerve injury, and the shape of the corner of the mouth was normal. The width and opening degree of oral fissure were not significantly reduced compared with those before operation. Meanwhile, the intraoral flap was thin and flat, and healed well with the surrounding mucosa, without obvious flap contracture, buccal bite, or incomplete closure. CONCLUSION: Overall, V-shaped folded nasolabial flap has the advantages of flexible design, simple preparation, reliable blood supply, and protection of the donor site, which may be one of the effective methods for repairing small-sized and medium-sized defects in the anterior buccal mucosa.

Systematic Analysis of tRNA-Derived Small RNAs Reveals the Effects of Xuefu-Zhuyu Decoction on the Hippocampi of Rats after Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases and refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu-Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic properties against TBI. Transfer RNA (tRNA)-derived small RNAs, that is, tsRNAs (a group of small RNAs derived from tRNAs), are multifunctional regulatory noncoding RNAs generated under pressure and implicated in the progression of TBI. Methods: A TBI model was successfully constructed using rats. We further performed sequencing and omics analyses to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in the rat hippocampus. qPCR assays were used to further verify the experimental results. Gene Ontology (GO) was used to analyze the signaling pathways of downstream target genes of tsRNAs in the XFZYD-regulated TBI model. qPCR was used to detect the influence of overexpressed tsRNA mimics/inhibitors on their target genes in PC12 cells. Results: Our RNA-Seq data illustrate that 11 tsRNAs were mediated by XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway. We also confirmed that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were target genes of 2 XFZYD-regulated tsRNAs in the hippocampus of a rat model and PC12 cells. Furthermore, biological function analysis revealed the potential therapeutic effects of tsRNAs, and the results showed that Mapk1 and Gnai1 were related genes for XFZYD therapy against TBI. Conclusion: Our work successfully illuminates the efficiency of XFZYD in the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway in a TBI rat model.

Shaoyao Gancao Decoction Ameliorates Paclitaxel-Induced Peripheral Neuropathy via Suppressing TRPV1 and TLR4 Signaling Expression in Rats.

Purpose: Paclitaxel-induced peripheral neuropathy (PIPN) is increasingly becoming one of the most widespread adverse effects in the treatment of cancer patients, and further precipitate neuroinflammation in the nervous system. Interestingly, Shaoyao Gancao Decoction (SGD), a traditional Chinese analgesic prescription, has emerged as a primary adjuvant to chemotherapy in relieving side effects, especially in the case of PIPN. However, the underlying mechanism of SGD functioning in PIPN remains elusive. Accordingly, the current study set out to explore the potential axis implicated in the functioning of SGD in PIPN. Methods: First, network pharmacology was adopted to predict the role of the transient receptor potential vanilloid type 1 (TRPV1) protein in treating PIPN with SGD. Subsequently, the effects of SGD treatment on mechanical allodynia and thermal hyperalgesia were evaluated in rat PIPN models. Based on the bioinformatics information and current literature, paclitaxel activates toll-like receptor 4 (TLR4) induces the sensitization of TRPV1 mechanistically. Thereafter, TLR4-myeloid-differentiation response gene 88 (MyD88) signaling and TRPV1 expression patterns in dorsal root ganglias (DRGs) were measured by means of Western blotting, qPCR and immunofluorescence. Results: Initial bioinformatics reared a total of 105 bioactive compounds and 1075 target genes from SGD. In addition, 40 target genes intersected with PIPN were considered as potential therapeutic genes. Based on the network analysis, SGD was found to exert its analgesic effect by reducing the expression of TRPV1. Further experimentation validated that SGD exerted an analgesic effect on thermal hyperalgesia in PIPN models, such that this protective effect was associated with the suppression of TRPV1 and TLR4-MyD88 Signaling over-expression. Conclusion: Collectively, our findings indicated that SGD ameliorates PIPN by inhibiting the over-expression of TLR4-MyD88 Signaling and TRPV1, and further highlights the use of SGD as a potential alternative treatment for PIPN.

Computer-assisted intraoral approach in the management of infected comminuted mandibular fractures: Technical notes.

In the extraoral approach for mandibular fractures, facial scars and facial nerve injury are common complications. Herein, we introduce an improved surgical technique to reduce fragments of infected comminuted mandibular fractures with the assistance of computer software. Firstly, the model was reset by 3-dimensional (3D) printing, and then the titanium plate was reconstructed on the model. Finally, open reduction and internal fixation through intraoral approach. This method can effectively control infection, reduce facial scars and avoid the risk of facial nerve injury.

Identification and Validation of a Novel Genomic Instability-Associated Long Non-Coding RNA Prognostic Signature in Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignant cancers worldwide, and accurate prognostic models are urgently needed. Emerging evidence revealed that long non-coding RNAs (lncRNAs) are related to genomic instability. We sought to identify and validate a genomic instability-associated lncRNA prognostic signature to assess HNSCC patient survival outcomes. Methods: RNA-sequencing data, somatic mutation files, and patient clinical data were downloaded from The Cancer Genome Atlas database. A total of 491 patients with completely clinical files were randomly divided into training and testing sets. In the training set, genomic instability-associated lncRNAs were screened through univariate Cox regression analyses and least absolute shrinkage and selection operator regression analyses to build a genomic instability-associated lncRNA signature (GILncSig). In addition, time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier survival curve, and clinical stratification analyses were used to evaluate the signature's reliability. Finally, in situ hybridization experiments were performed to validate GILncSig expression levels between adjacent non-tumor tissues and tumor tissues from HNSCC patients. Results: Four genomic instability-associated lncRNAs (AC023310.4, AC091729.1, LINC01564, and MIR3142HG) were selected for the prognostic signature. The model was successfully validated using the testing cohort. ROC analysis demonstrated its strong predictive ability for HNSCC prognosis. Univariate and multivariate Cox analyses revealed that the GILncSig was an independent predictor of prognosis. HNSCC patients with a low-risk score showed a substantially better prognosis than the high-risk groups. The in situ hybridization experiments using human HNSCC tissue revealed high GILncSig expression in HNSCC tissues compared with adjacent non-tumor tissues. Conclusion: We developed a novel GILncSig for prognosis prediction in HNSCC patients, and the components of that signature might be therapeutic targets for HNSCC.

Modified V-Y Myocutaneous Flap With Vascular Pedicle for the Repair of Maxillofacial Skin Defects.

OBJECTIVE: It is challenging to repair postoperative defect caused by skin tumor resection on the maxillofacial, which not only affects appearance but also impairs functions. To better repair skin defect on the maxillofacial, the application value of V-Y vascular myocutaneous flap was introduced in our study. METHODS: Between June 2011 and December 2018, 16 patients with maxillofacial skin tumors who received extensive resection were enrolled in our study. The defect on the maxillofacial was repaired by V-Y vascular myocutaneous flap. The follow-up period lasted for 12 to 24 months. RESULTS: All 16 cases of myocutaneous flaps survived with 1 case of partial venous congestion and 1 case of partial distal necrosis. No recurrence occurred during follow-up. The color and texture of myocutaneous flaps like those of the surrounding skin. CONCLUSION: Featured with better freeness, larger repair range and aesthetic effect of "kite" flaps, V-Y vascular myocutaneous flap can repair the superior border of zygomatic arch pedicled with facial artery and repair 1.5 cm above the superior border of zygomatic arch pedicled with transverse facial artery for elderly patients in Asia.

Preliminary application and evaluation of autograft reconstruction of parotid duct defect with submandibular gland duct for buccal cancer.

Background: We aimed to preserve parotid function in patients with buccal carcinoma by applying a new surgical protocol based on reconstruction of parotid ductal defect with submandibular gland ductal.Aims/Objectives: The aim of this study is to introduce the method of autologous submandibular gland duct reconstruction for the treatment of parotid duct defect in buccal carcinoma, and to evaluate its clinical application in follow-up.Material and methods: A total of 28 patients with buccal carcinoma who underwent buccal and neck combined with radical surgery and vascularized flap transplantation were enrolled. Function of the reconstructed duct was reviewed in 6 months after surgery.Results: Both groups achieved good short-term results within 1 month after surgery. The 6-month postoperative angiography examination of the submandibular gland duct showed that 6% of patients in the submandibular gland duct graft group had a blockage or was not smooth. At the same time, 45% of the patients in the vein graft group had failure or obstruction, and the VAS score of pain was higher than that of the submandibular gland ductal graft group (p < .05).Conclusion and significance: Compared with vein grafting, the reconstruction of parotid ductal defect with submandibular gland ductal graft has better long-term effects.

The Efficacy and Safety of Submandibular Transcatheter Perfusion Anesthesia in Submandibular Gland Surgery.

The present study aims to evaluate the feasibility, safety, and effects of the combined use of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration for anesthetic purposes during submandibular gland surgery. A total of 38 patients with benign tumors, who had undergone resection by submandibular gland surgery were randomly divided into 2 groups. Patients in group A were administered with submandibular anesthesia through catheter perfusion, lingual nerve block, and subcutaneous infiltration anesthesia. Patients in the group B were only treated with lingual nerve block and subcutaneous infiltration anesthesia. The submandibular gland surgery was performed within 5 minutes following anesthesia administration, after which the numerical rating scale (NRS) was evaluated before surgery, during skin incision (T1), during the pulling process of the submandibular gland (T2), during the removal of the submandibular gland (T3), and at 2, 6, 12, and 24 hours post-surgery. The dosage of analgesic drugs was also measured after surgery. The findings revealed no significant difference in NRS before surgery, at T1, 6, 12, and 24 hours after surgery (P > 0.01) while NRS was much lower in group A patients as observed at T2, T3, and 2 hours after surgery when compared with group B (P < 0.01). The combined application of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration can be used as an effective anesthetic method during submandibular gland surgery.

MiR-199a-5p represses the stemness of cutaneous squamous cell carcinoma stem cells by targeting Sirt1 and CD44ICD cleavage signaling.

Tumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitro and in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8.

Herb-Drug Interaction Potential of Licorice Extract and Paclitaxel: A Pharmacokinetic Study in Rats.

BACKGROUND AND OBJECTIVES: Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb-drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. METHODS: A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). RESULTS: The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC0-t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC0-t (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05). CONCLUSIONS: The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.

Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome.

Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.

Pretreatment of Shaoyao Gancao Decoction () alters pharmacokinetics of intravenous paclitaxel in rats.

OBJECTIVE: To investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats. METHODS: Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0. RESULTS: The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC0-t, from 4 820±197 to 4 205±186 ng·mL-1·-1) and AUC0-∞ (from 5 237±280 to 4 514±210 ng·mL-1·-1) significantly decreased in response to the 14-day pretreatment with SGD. The values of Vdss (L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t1/2 (h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUC0-t and AUC0-∞ values decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel. CONCLUSIONS: SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.

An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma.

Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltrating-lymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center-like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of antigen-experienced CD4+ and CD8+ cells were present, as well as an enrichment of regulatory T cells; and T cells expressing programmed death-1 (PD-1) and T cell Ig and mucin protein-3 (Tim-3), indicative of exhaustion, within the tumor microenvironment. Characterization of tumor-infiltrating B cells revealed clear evidence of antigen exposure, in that the cardinal features of an antigen-driven B cell response were present, including somatic mutation, clonal expansion, intraclonal variation and isotype switching. Collectively, our results point to an adaptive immune response occurring within the OSCC microenvironment, which may be sustained by the expression of specific antigens in the tumor.

[Myoepithelial carcinoma of salivary glands: a clinical analysis of 13 cases].

PURPOSE: This study retrospectively analyzed the clinical data of 13 patients with myoepithelial carcinoma of salivary glands for improving the accuracy of diagnosis and treatment outcome. METHODS: Thirteen cases with myoepithelial carcinoma of the salivary glands in Xiangya Hospital from January 1992 to September 2010 were reviewed, including the clinical biological behavior, diagnosis,treatment and prognosis. RESULTS: Thirteen patients included 6 men and 7 women, aged from 14 to 71 years (median 40 years).The tumor occurred predominantly in the parotid gland (53.8%).Among the 13 cases,7 were clinically misdiagnosed as benign tumors and 2 were misdiagnosed pathologically. All cases underwent operation. Two cases received surgery plus adjuvant chemotherapy; five cases underwent surgery plus adjuvant radiotherapy. 4(30.8%) had cervical lymph node metastasis and 2 cases(15.4%) developed distant metastasis. Follow-up time ranged from 3 months to 6 years. Six cases died of local recurrence or distal metastasis. CONCLUSIONS: Myoepithelial carcinoma of the salivary glands is a rare tumor. The diagnosis is depended on histology and immunohistochemistry. The tumor has a high rate of distant metastasis and high rate of lymph node metastasis in T3 to T4 cases. Radical surgery is the treatment of choice. Elective neck dissection should be considered in T3 to T4 cN0 cases. The effect of chemotherapy and radiotherapy needs to be investigated.