硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺方案治疗多发性骨髓瘤

目的 观察硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺(V-CMPT方案)治疗多发性骨髓瘤(MM)的临床疗效和患者不良反应.方法 回顾性分析应用V-CMPT方案进行治疗的24例初治和复发难治MM患者资料,3周为1个周期,治疗2个周期.应用骨髓细胞学检查、M蛋白鉴定以及其他血液学指标评价病情及疗效.结果 初治的9例患者中,完全缓解(CR)3例、部分缓解(PR)5例、轻微缓解(MR)1例;复发难治的15例患者中,CR2例、接近完全缓解(nCR)2例、PR 3例、MR 6例、无变化(NC)2例;两组间总缓解率(ORR)(P=0.511)及CR/nCR率(P=1.000)差异无统计学意义.总的CR/nCR率29.2%(7/24),ORR达到91.7%(22/24).2个周期V-CMPT化疗后,患者的血红蛋白、血清清蛋白及血清β2微球蛋白得到明显改善.不良反应包括胃肠道反应、血小板减少、周围神经病变等,经对症处理或间歇期停药多好转,不影响化疗的继续进行.结论 V-CMPT方案对初治和复发难治性MM临床疗效明显,能够明显改善血液学指标,药物耐受性良好.     

乳腺癌新辅助化疗前后HER-2表达的变化

Objective: The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases. Methods: One hundred and thirty-seven female patients with primary breast cancers, who received neoadjuvant chemotherapy, underwent core needle puncture and Mammotome biopsy before chemotherapy, and the biopsy results were used as the basis of histological diagnosis, fluorescence in situ hybridization (FISH) was performed to test HER 2 status of tumor tissues before and after chemotherapy. All patients underwent FEC, TE, or AC neoadjuvant chemotherapy of 2-6 cycles before surgery. Results: Twenty-two patients were positive according to FISH test among 137 preoperative patients, 8 patients achieved pathological complete remission after chemotherapy (three HER-2 positive patients and five negative patients), 91 patients achieved partial remission, 24 patients were stable, and 14 cases were invalid. Twenty-two patients were positive according to FISH test (8 patients with pathological complete remission did not undergo test), and positive patients still expressed positively after chemotherapy before neoadjuvant chemotherapy. Three negative patients were converted to be positive, and changes before and after chemotherapy had no statistical difference (P > 0.05). Conclusion: Neoadjuvant chemotherapy makes no influence on patients with HER-2 positive expression, while patients with negative expression can be converted to be positive, but without significant difference.     

三维适形放疗配合腔内后装治疗宫颈癌的临床研究

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total close of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median close of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%,70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups.Compared to the two groups each other in toxic effects, except for the Ⅰ-Ⅱ grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new rote for 3DCRT merits need further evaluation with large patient numbers and longer follows up.     

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.     

RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA

Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug's ability to silence expression suppresses the growth of cholangiocarcinoma cells and/or sensitizes cholangiocarcinoma cells to chemotherapeutic agents through induction of apoptosis. We targeted the Slug gene using siRNA (Slug siRNA) via full Slug cDNA plasmid (Slug cDNA) transfection of cholangiocarcinoma cells. Slug siRNA, cisplatin, or Slug siRNA in combination with cisplatin, were used to treat cholangiocarcinoma cells in vitro. Western blot was used to detect the expression of Slug, PUMA, and E-cadherin protein. TUNEL, Annexin V Staining, and cell cycle analysis were used to detect apoptosis. A nude mice subcutaneous xenograft model of QBC939 cells was used to assess the effect of Slug silencing and/or cisplatin on tumor growth. Immunohistochemical staining was used to analyze the expression of Slug and PUMA. TUNEL was used to detect apoptosis in vivo. The results showed that PUMA and E-cadherin expression in cholangiocarcinoma cells is Slug dependent. We demonstrated that Slug silencing and cisplatin both promote apoptosis by upregulation of PUMA, not by upregulation of E-cadherin. Slug silencing significantly sensitized cholangiocarcinoma cells to cisplatin through upregulation of PUMA. Finally, we showed that Slug silencing suppressed the growth of QBC939 xenograft tumors and sensitized the tumor cells to cisplatin through PUMA upregulation and induction of apoptosis. Our findings indicate that Slug is an important modulator of the therapeutic response of cholangiocarcinoma cells and is potentially useful as a sensitizer in cholangiocarcinoma therapy. One of the mechanisms is the regulation of PUMA by Slug.     

Garlic Oil Suppressed the Hematological Disorders Induced by Chemotherapy and Radiotherapy in Tumor‐Bearing Mice

Although the anticancer effects of garlic and its products have been demonstrated by a variety of studies; however, few studies were conducted to investigate the effects of garlic on the adverse effects of chemo/radiotherapy. In order to clarify the above question and make a more comprehensive understanding of the anticancer effects of garlic, tumor xenograft mice model was established by subcutaneous injection of H22 tumor cells, and was used for the investigation of effects of garlic oil (GO) on the chemo/radiotherapy. In the chemotherapy test, tumor‐bearing mice were treated with cyclophosphamide (CTX) or CTX plus GO (25 or 50 mg/kg bw) for 14 d, while the mice received a single 5 Gy total body radiation or radiation plus GO (25 or 50 mg/kg bw) in radiotherapy test. The results showed that GO did not increase the tumor inhibitory rate of CTX/radiation, which indicated that GO could not enhance the chemo/radiosensitivity of cancer cells. However, the decrease of the peripheral total white blood cells (WBCs) count induced by CTX/radiation was significantly suppressed by GO cotreatment. Furthermore, GO cotreatment significantly inhibited the decrease of the DNA contents and the micronuclei ratio of the bone marrow. Lastly, the reduction of the endogenous spleen colonies induced by CTX/radiation was significantly suppressed by GO cotreatment. These findings support the idea that GO consumption may benefit for the cancer patients receiving chemotherapy or radiotherapy.     

射频透热联合化疗治疗恶性胸腔积液的临床评价

目的: 为了改善晚期肿瘤患者生活质量, 观察局部射频透热化疗治疗恶性胸腔积液患者的临床疗效。方法: 60 例恶性胸腔积液患者在全身化疗后采用胸腔穿刺, 中心静脉导管置入胸腔持续闭式引流排胸液。随机分成2 组, 热化疗组和化疗组。采用胸腔灌注顺铂60 mg, 2 周1 次, 其中热化疗组于灌注顺铂30 min 内进行胸部射频透热治疗60 ～ 90 min 次, 每周2 次, 热疗8 ～ 10 次。结果: 化疗组有效率67 %, 热化疗组有效率90 %, 显著高于化疗组(P<0. 05)。热化疗组生活质量评分(KPS)高于化疗组(P<0. 01)。不良反应基本相似。结论: 射频透热联合双途径化疗是目前治疗恶性胸腔积液患者有效、可行的一种方法。     

Fluorescent Imaging‐Guided Chemotherapy‐and‐Photodynamic Dual Therapy with Nanoscale Porphyrin Metal–Organic Framework

Imaging‐guided therapy systems (IGTSs) are revolutionary techniques used in cancer treatment due to their safety and efficiency. IGTSs should have tunable compositions for bioimaging, a suitable size and shape for biotransfer, sufficient channels and/or pores for drug loading, and intrinsic biocompatibility. Here, a biocompatible nanoscale zirconium‐porphyrin metal–organic framework (NPMOF)‐based IGTS that is prepared using a microemulsion strategy and carefully tuned reaction conditions is reported. A high content of porphyrin (59.8%) allows the achievement of efficient fluorescent imaging and photodynamic therapy (PDT). The 1D channel of the Kagome topology of NPMOFs provides a 109% doxorubicin loading and pH‐response smart release for chemotherapy. The fluorescence guiding of the chemotherapy‐and‐PDT dual system is confirmed by the concentration of NPMOFs at cancer sites after irradiation with a laser and doxorubicin release, while low toxicity is observed in normal tissues. NPMOFs are established as a promising platform for the early diagnosis of cancer and initial therapy.     

Neurotoxicity Associated with Treatment of Acute Lymphoblastic Leukemia Chemotherapy and Immunotherapy

Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. Acute neurological complications occur in 3.6–11% of children treated for ALL. The most neurotoxical chemotherapeutics are L-asparaginase (L-ASP), methotrexate (MTX), vincristine (VCR), and nelarabine (Ara-G). Neurotoxicity associated with methotrexate (MTX-NT) occurs in 3–7% of children treated for ALL and is characterized by seizures, stroke-like symptoms, speech disturbances, and encephalopathy. Recent studies indicate that specific polymorphisms in genes related to neurogenesis may have a predisposition to MTX toxicity. One of the most common complications associated with CAR T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS). Mechanisms of neurotoxicity in CAR T-cell therapy are still unknown and may be due to disruption of the blood–brain barrier and the effects of elevated cytokine levels on the central nervous system (CNS). In this review, we present an analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL.