Effect of mebendazole againstEchinococcus granulosus andTaenia hydatigena cysts in naturally infected sheep and relevance to larval tapeworm infections in man

The ability of three treatment schedules of mebendazole to kill well-established hydatid cysts was studied. Pregnant sheep, naturally infected withEchinococcus granulosus and/orTaenia hydatigena, were treated daily with mebendazole at a dose rate of 50 mg/kg body weight for either five days, one month, or three months.At autopsy, seven months after the commencement of treatment, no evidence was found that the 5-day treatment schedule had any damaging effect onE. granulosus cysts. The effects of the one month treatment were equivocal. There was evidence of a damaging effect from the 3-month treatment schedule and protoscoleces were not infective to dogs. NoT. hydatigena cysts survived the 1- and 3-month treatments, but organisms from the 5-day treatment were infective to dogs.These results forE. granulosus in sheep suggest that long-term treatment with mebendazole may be required in hydatid disease in man. The results obtained forT. hydatigena in sheep are discussed in relation to the treatment of cysticercosis fromT. solium in man. Mebendazole showed no untoward effect on the sheep or their lambs.     

Chemotherapy of fish parasites

There are few agents on the market that control fish parasites. These are substances that are mainly used in other hosts; due to the different metabolism of fish, they often have only moderate effects on fish parasites. Therefore, the research and development of fish-specific antiparasitic compounds is needed to avoid the high losses suffered by commercial fish hatcheries. Drugs similar to toltrazuril would perhaps be promising, due to their broad spectrum of efficacy.     

Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat

Abstract Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21^waf1/cip1 (p21) were examined quantitatively. Data were analysed using Peritz F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells.     

Preliminary report on AT1727 as a potential radiosensitizer

AT1727 is a derivative of ICRF 154. The purpose of this study was to evaluate its "radiosensitizer" properties. From October 1979 until the end of December 1980, 89 patients with radiation resistant cancers such as soft tissue sarcoma, squamous lung cancer (with large lesion, 6-8 cm diameter) and other cancers had been included in trial. Radiation therapy was carried out using CO60 or 8 Mev Linac. Fifty-five patients had a remarkable objective remission rate of 61.8% (55/89). Eighteen of 30 patients with soft tissue sarcomas obtained obvious remission (60%), and 26 of 38 patients with lung cancer had remission (68.4%). Patients with esophageal cancer (5/6) and nasopharyngeal cancer (5/5) also had good remission rates. The side-effects of this treatment were very mild: anorexia and vomiting were noted in 50% and no significant changes were noted in liver and kidney function tests and blood platelet count. Leucopenia was slight in all but one patient. No difference in the lung fibrosis rate was noted between the two randomized groups. From the results of this study we concluded that AT1727 had some effect as a "radiosensitizer" but much more work is needed to confirm this.     

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India

BackgroundYoung (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying.MethodsThe YBC treated with a curative intent between 2015 and 2016 at our institute were analysed.ResultsThere were 1228 patients with a median age of 36 (12–40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) –III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0–131) months, 5-year overall and disease-free survival was 79.6% (76.8–82.5) and 59.1% (55.8–62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8–90.6), 77.3% (73.4–81.2), 69.7% (52.5–86.9) and disease-free survival was 94% (85.9–100), 65.9% (60.3–71.5), 55% (50.5–59.5), and 29.6% (14–45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6–86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients.ConclusionMore than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.     

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.     

Ivermectin levels in human breastmilk

Summary Ivermectin levels were measured in breastmilk and plasma of 4 healthy mothers after an oral 150 g/kg dose. Mean ± S.D. plasma and milk values were 37.9±0.54 and 14.13±0.43 (ng/ml) respectively. Steady-state ivermectin levels in milk were low. Our results suggest that exclusion of lactating mothers from mass chemotherapy with ivermectin may be unnecessary.     

口腔颌面鳞癌术前诱导化疗二种方式临床疗效分析

目的 :探讨口腔颌面鳞癌术前诱导化疗二种方式应用的疗效、主要毒副反应差别 ,以及临床适应证。为术前诱导化疗的选择提供临床指导。方法 :本文回顾了 1 0 4例可评价近期疗效的口腔颌面鳞癌术前诱导化疗的病例。其中全身化疗 5 6例 ,颈外动脉插管化疗 48例。结果 :以肿瘤体积缩小 5 0 %以上作为化疗有效指标 ,全身化疗组有效率为 6 4.3%。颈外动脉插管化疗组有效率为79.2 % ,两组总有效率为 71 .2 % (P<0 .0 5 )。全身化疗组的主要毒副反应为胃肠反应、白细胞减少和脱发 ;颈外动脉插管化疗组主要为口腔粘膜溃疡、糜烂及灼痛感。结论 :作为术前诱导的全身化疗较适合于全身状况良好的患者 ,而颈外动脉插管灌注化疗较适合于全身状况稍差、无转移、肿瘤范围不广的患者。     

HNE1细胞株光动力学治疗前后形态学的动态变化

目的 探讨体外光动力学治疗（ＰＤＴ）引起鼻咽癌（ＮＰＣ）细胞死亡的作用机制。方法对鼻咽癌细胞株ＨＮＥ１体外光动力学治疗前后形态学变化进行动态观察。结果 对照组ＨＮＥ１细胞培养３ｈ,６ｈ,１２ｈ,２４ｈ和４８ｈ后细胞形态与正常培养组ＨＮＥ１细包开始变形皱缩,细胞界限模糊,细胞透光度和立体感较差,治疗２４～４８ｈ后细胞发生凋亡。结论 体外光动力学治疗对ＨＮＥ１具有明显的杀伤效应并ＨＮＥ１细胞凋亡。ＰＤ