Inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer

Progestin resistance is the main obstacle to successful conservative therapy in young endometrial cancer patients. To investigate the molecular events that lead to progestin resistance and to find a possible way to reverse progestin resistance in endometrial cancer, we established a progestin-resistant Ishikawa cell line by long-term progestin treatment to downregulate progesterone receptor (PR) expression. Both medoxyprogesterone acetate (MPA) and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, were assayed for their effects on the proliferation of progestin-sensitive and progestin-resistant cancer cells, respectively. The MPA inhibited the PI3K/Akt pathway and suppressed cell proliferation in progestin-sensitive Ishikawa cells, but activated the PI3K/Akt pathway and had no effect on cell proliferation in progestin-resistant Ishikawa cells or HEC-1A cells. Inhibiting the PI3K/Akt pathway by LY294002 upregulated PR expression and diminished cell growth, especially in progestin-resistant endometrial cancer cells. In vivo endometrial cancer xenograft studies in nude mice also showed that inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer. Our results indicate that activation of the PI3K/Akt pathway by progestin without PR mediation plays an important role in progestin resistance to endometrial cancer cells. In addition, inhibiting the PI3K/Akt pathway might reverse progestin resistance in endometrial cancer.     

Relationship Between CT Volumetry and Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization Before Major Hepatectomy: A Preliminary Study

To clarify the relationship between morphological measurements of hepatic volume by computed tomography (CT-vol) and functional volume (RI-vol) by technetium-99m galactosyl human serum albumin (^99mTc-GSA) scintigraphy, and its clinical significance, we examined 16 patients with a background liver status of either normal liver function (n = 4), chronic hepatitis or cirrhosis (n = 7), or obstructive jaundice (n = 5). In five patients who underwent preoperative portal vein embolization (PVE), volumetric measurement was performed 2 weeks after PVE. The mean values of CT-vol and RI-vol of the right lobe were 692± 147 cm³ (66.1 ± 10.7%) and 668 ± 159 cm³ (67.8 ± 13.2%), respectively, and those of the left lobe were 329 ± 138 cm³ (33.9 ± 10.6%) and 328± 170 cm³ (32.2 ± 13.2%), respectively. There were no significant differences in the volume measurements between the two volumetric techniques. Correlations between CT-vol and RI-vol in the right and left lobes were positive and significant (r = 0.912 and 0.903, respectively; both P′s < 0.001). The mean values of post-PVE CT-vol and RI-vol of the right lobe in five patients were significantly different (628 ± 149 and 456± 211 cm³, respectively; P = 0.033). However, the mean values of post-PVE CT-vol and RI-vol of the left lobe were not different (496 ± 124 and 483± 129 cm³, respectively). We propose that volumetric measurement by ^99mTc-GSA scintigraphy is useful for detecting changes in functional volume of individual lobes of the liver and is a more dynamic method compared with detection of morphological changes by CT scan. No financial support was received from any source for this study.     

开颅术后颅内压监测下继发颅内感染的危险因素及防治措施

目的探讨开颅术后颅内感染发生的易感因素及防治措施。 方法选取自2010年8月至2014年8月凉山彝族自治州第一人民医院神经外科收治的颅脑术后发生颅内感染的21例患者的临床资料进行分析,采用t检验和logistic回归分析方法研究各因素与颅内感染的关系。 结果单因素分析结果显示,颅内感染的发生与年龄（≥70岁）、术前GCS评分（≤8分）、是否合并糖尿病、手术时间（>4 h）、颅内压监测天数（>7 d）等因素有相关性,差异具有统计学意义（P<0.05）;进一步通过多因素logistic回归分析发现,年龄（≥70岁）、术前GCS评分（≤8分）、手术时间（>4 h）、颅内压监测天数（>7 d）是颅脑手术颅内压监测下继发颅内感染的独立危险因素。 结论加强老年患者的营养支持,尽量缩短手术时间,尽早拔除颅内压传感器,严格无菌操作,是有效预防颅内感染的重要措施。     

Interactive-plan technique conquers the disadvantages of volume-reducing hormone therapy in 125I permanent implantation for localized prostate cancer

Background  The purpose of this study was to assess the impact of hormone therapy on post-implant dosimetry in patients in whom pre-plan and interactive-plan techniques were used for transperineal brachytherapy against prostatic cancer. Methods  The subjects comprised 244 patients treated using ¹²⁵I seed implantation as monotherapy. The prescribed dose to the periphery of the prostate was 145 Gy. The pre-plan technique was used for 116 patients, and the interactiveplan technique for 128 patients. Hormone therapy was used in 71 patients (29.1%). The D90 (dose to 90% of prostate volume) of post-implant computed tomography (CT) analysis was assessed in both groups. In addition, the ratio of post-implant CT volume to preoperative ultrasonography (US) volume was assessed. Results  In the pre-plan group, D90 was significantly lower for patients who received hormone therapy than for those who did not (P = 0.035). However, in the interactive-plan group, D90 did not differ between patients with and without hormone therapy (P = 0.467). The CT-to-US prostate volume ratio was 1.022 for patients who received hormone therapy and 0.960 for patients who did not (P = 0.021). Conclusion  Post-traumatic swelling following implantation is increased by cessation of hormone therapy and may reduce D90. However, the present results suggest that the interactive-plan technique overcomes this disadvantage of hormone therapy.     

Serum interleukin-6 and -10 levels in patients with gastric cancer

Background  Interleukin-6 (IL-6) is known to be a multifunctional cytokine and IL-10 is an immunosuppressive factor. Both have been reported to be related to the disease prognosis in some human solid tumors. In the present study, we evaluated the clinical significance of preoperative serum IL-6 and IL-10 levels as new tumor markers in patients with gastric cancer (GC). Methods  Preoperative serum samples from 90 patients with GC and 9 normal healthy volunteers were assayed. Levels of IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The clinical significance of serum IL-6 and IL-10 levels was evaluated and compared with serum carcinoembryonic antigen (CEA) levels and serum C-reactive protein (CRP) levels in these patients. Results  The serum level of IL-6 was significantly higher in the GC patients than in the healthy subjects. Serum IL-6 levels were strongly correlated with CRP levels, but did not correlate with CEA or carbohydrate antigen (CA) 19-9 levels. Serum IL-10 levels did not correlate with CEA, CA19-9, or CRP. Strong positive correlations between serum IL-6 levels and tumor size and tumor stage were observed. On the other hand, IL-10 did not correlate with such clinicopathological findings of tumors. However, high serum IL-10 levels were associated with a worse prognosis in the GC patients, independently of their tumor stage. Conclusion  These findings indicate that serum IL-6 may suggest gastric cancer progression. On the other hand, IL-10 may play an important role in host immunity and the prognosis of GC patients.     

RPS2: a novel therapeutic target in prostate cancer

Background

A number of studies have previously shown that the over expression of different ribosomal proteins might play an important role in cancer (i.e. S3a, L10, L16). We have previously reported that RPS2, a 33 Kda ribosomal protein was over expressed in malignant prostate cancer cell lines and in archived tumor specimens. Thus, RPS2 or other aberrantly over-expressed ribosomal proteins might promote cancer and be excellent therapeutic targets for treatment of the disease.

Methods

Western blotting and RT-PCR have been used to measure and compare the levels of expression of RPS2 in a variety of malignant prostate cancer cell lines, plus normal and benign cells lines. We have developed a ''ribozyme-like'' DNAZYM-1P ''10–23'' motif oligonucleotide and examined whether it targets RPS2 in different cell lines by RT-PCR and Western blots. Growth and apoptosis assays were carried out to measure whether DNAZYM-1P ''knock-down'' of RPS2 influenced cell proliferation or survival. We have also developed a SCID mouse tumor model with PC-3ML cells to determine whether DNAZYM-1P targeting of RPS2 compromised tumor growth and mouse survival rates in vivo.

Results

Western blots showed that PC-3ML, LNCaP, CPTX-1532, and pBABE-cmyc stably transfected IBC-10a cells all over-expressed RPS2, whereas IBC-10a parent, NPTX-1532, and BPH-1 cells or mouse NIH-3T3 cells expressed barely detectable levels of RPS2. RT-PCR assays showed that DNAZYM-1P, which targeted RPS2, ''knocked-down'' RPS2 expression in the malignant cells (i.e. PC-3ML cells) in vitro. The DNAZYM-1P also inhibited cell growth and induced apoptosis in the malignant prostate cells, but had little effect on the normal IBC-10a or NPTX-1532 cell lines. Finally, SCID mouse tumor modeling studies showed that DNAZYM-1P blocked tumor growth and metastasis by PC-3ML cells and eventually eradicated tumors following localized or systemic i.v. delivery. Mouse survival studies revealed that there was a dosage dependent increase in disease free survival rates in mice treated systemically with DNAZYM-1P (i.e. mouse survival increased from 0% to 100%).

Conclusion

In sum, we have shown for the first time that therapeutic targeting of RPS2 is an excellent approach for the eradication of prostate cancer in preclinical tumor modeling studies.     

中医“肾髓系统”刍议

肾藏精,精生髓,髓充脑、养骨、生血,"肾、精、髓"物质与功能共同构成了中医"肾髓系统",其中"肾为本,精为要,髓为枢",肾中精气盛衰决定髓的盈亏,是脑为髓海、肾主骨、精化血的生理和病理基础;同时,中医现代研究发现干细胞与肾精关系密切,体现了"肾髓系统"的物质和功能特点。     

尼妥珠单抗同步调强放射治疗对老年局部晚期子宫颈癌的安全性和有效性研究

目的 探讨尼妥珠单抗联合放疗对老年局部晚期子宫颈癌患者的安全性和有效性。方法 回顾性分析福建医科大学附属漳州市医院2020年6月至2021年12月共34例尼妥珠单抗联合调强放疗或同步放化疗治疗老年局部晚期子宫颈癌患者。评价治疗后1年和2年疗效及不良反应。结果 中位随访时间13.3个月(6.1~24.3个月)。全组完全缓解(CR)24例,部分缓解(PR)8例,客观缓解率(ORR)为94.1%(32/34)。放疗前肿瘤直径(49.56±19.22) mm,尼妥珠单抗联合外照射后,肿瘤直径(19.61±14.59) mm,肿瘤退缩率(TRR)59.22%。1、2年无进展生存率(PFS)分别为84.9%、84.9%,1、2年总生存率(OS)分别为91.8%、87.2%。1、2年无病生存率(DFS)分别为91.8%、87.2%,肿瘤特异性生存率(CSS)分别为95.7%、90.9%。主要不良事件为放射性肠炎、白细胞减少、低蛋白血症、贫血。结论 尼妥珠单抗联合放疗/同步放化疗治疗老年局部晚期子宫颈癌安全有效。