Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma

Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic‐resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3 g of methenamine iodomethylate and 1 g of methenamine sodium benzoate in 100 cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic pH, it would be plausible to expect that methenamine would selectively target dormant, non‐proliferative, and treatment‐resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.     

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression-free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry-based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26–0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31–0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry-defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab.     

A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.     

Prostate Radiotherapy in India: Evolution,Practice and Challenges in the 21st Century

The practice of prostate radiotherapy is evolving rapidly while there is an increase in the incidence of prostate cancer in India. Here, the diverse socioeconomic milieu and varied healthcare delivery models interact to exert a significant influence on the adoption of new technologies and evidence emerging from the Western world. Using a targeted cross-country survey of radiation oncologists, this article captures the changing trends in prostate imaging, conformal techniques, dose escalation, hypofractionation, stereotactic ablation and prostate brachytherapy in the context of practice patterns in the West. New directions in research on prostate cancer are highlighted, reflecting the unique challenges of the disease profile and treatment resources in India.     

Prognostic significance of number versus location of positive mesenteric nodes in stage iii colon cancer

IntroductionDebate persists on the ideal extent of lymphadenectomy for colon cancer (CC). Specifically, it is unknown whether the anatomical location of positive lymph nodes (LN) has any independent prognostic significance. We assessed the prognostic value of positive LN location in stage III CC patients who underwent extensive (D3) lymphadenectomy.MethodsPatients from Kanagawa Cancer Center, Japan, who underwent D3 dissection for CC from 2000 to 16 were analyzed. Mesenteric LN were classified according to location as paracolic (L1), intermediate (L2), or central (L3). Recurrence-free survival (RFS) and the corresponding hazard function were evaluated with their trends over the L groups. Multivariate Cox models were used to evaluate the association of LN location with RFS.ResultsFour hundred forty-six stage III patients were analyzed. The mean number of examined/positive nodes per patient was 42.5/2.6 in L1 (n = 310), 40.9/4.8 in L2 (n = 111), and 44.0/9.8 in L3 (n = 25). RFS was worse for L3 vs. L2 (HR: 2.00, 95%CI [1.05–3.75], p = 0.034) and for L3 vs. L1 (2.62 [1.45–4.71], p = 0.001), but not significantly different between L2 and L1 (1.32 [0.89–1.5], p = 0.17). In a multivariate model adjusting for age, tumor size, and number of lymph nodes harvested T-stage (p < 0.001), adjuvant therapy (p < 0.0038), lymphatic invasion (p = 0.023), and LNR (p = 0.038) were significantly associated with RFS, but not L level or tumor location.ConclusionThe anatomical location of invaded LN does not significantly correlate with RFS in CC, after adjusting for potential confounders. Central LN are infrequently invaded and confer a worse RFS.     

Elevated Serum Cytokines and Trichomonas vaginalis Serology at Diagnosis Are Not Associated With Higher Gleason Grade or Lethal Prostate Cancer

Background

Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.

滋阴化痰方联合化疗治疗晚期胃癌的疗效观察

目的 探究滋阴化痰方联合化疗治疗晚期胃癌的临床疗效。方法 以2011年3月~2017年10月痰瘀互结证晚期胃癌患者为研究对象,采用随机数字表法将其分为化疗组和中西医结合组,各40例。化疗组首先选用SOX方案,完成2个周期的治疗后,疾病进展者换用S-1+Docetaxel或CapeOX为主的方案治疗。中西医结合组在化疗基础上联用滋阴化痰方。比较两组疾病控制率(DCR)、客观有效率(RR)及治疗前后中医证候积分、Karnofsky活动状况量表(KPS)评分；观察两组患者治疗前后免疫功能指标及肿瘤炎性因子水平变化情况,并统计两组治疗后3年的生存情况。结果 中西医结合组RR高于化疗组(P<0.05),两组DCR对比无明显差异(P>0.05)；中西医结合组治疗后中医证候积分评分低于化疗组,KPS评分高于化疗组(P<0.05)；中西医结合组治疗后缺氧诱导因子-1α(HIF-1α)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、单核细胞趋化蛋白-1(MCP-1)水平低于化疗组(P<0.05)；中西医结合组治疗后CD3_⁺、CD4_⁺、CD4_⁺/CD8_⁺值大于化疗组(P<0.05)；两组1年、2年、3年生存率对比无明显差异(P>0.05),中西医结合组与化疗组中位OS分别为20.15、16.7个月。结论 滋阴化痰方联合化疗治疗晚期胃癌不仅能提高临床疗效,改善患者免疫功能,减轻炎症反应,还能提高患者生活质量,并能延长生存期。     

Breast Cancer Management During COVID-19 Pandemic in Madrid: Surgical Strategy

BackgroundFrom the first case of SARS-CoV-2 infection in Wuhan (China), the infection spread all around the world causing a pandemic of coronavirus disease-2019 (COVID-19). Spain has been one of the most severely affected countries, and Madrid has reported a high number of cases and deaths. We discuss our strategies for optimal breast cancer management during COVID-19 pandemic.Patients and MethodsThis was a retrospective observational study at Clínico San Carlos Hospital to analyze the management of patients with breast cancer during the pandemic outbreak and the surgical strategy after the pandemic outbreak. We created a practical and dynamic tool based on a “traffic light” system for prioritizing surgical time. Every patient was contacted by telephone with a preoperative COVID-19 protocol. After surgical procedures, patient satisfaction was assessed using the European Organisation for Research and Treatment of Cancer in-patient satisfaction with cancer care questionnaire (EORTC IN-PATSAT32).ResultsPatients with breast cancer actively treated with surgical procedures were put on a waiting list and received systemic therapy. Telemedicine was used to evaluate any side effects and to avoid unnecessary hospital visits. Surgery was only considered after the pandemic outbreak, and then, only those procedures designed to minimize surgical complications and, therefore, reduce hospital stay. We also measured patients’ satisfaction with medical and nursing scales that resulted in a “very good” evaluation tending to “excellent”.ConclusionIt is necessary to adapt management of oncology treatment and surgical strategy to optimize resources during the COVID-19 pandemic. Patients’ perception of care quality and the degree of patients’ satisfaction with health services has potential relevance in the absence of outcome data.