Ciência e terapia do câncer

Objective: Intranasal route is an emerging option for brain cancer treatment to infuse directly telomerase inhibitors and/or viruses into the brain. Paradoxically, the standard chemotherapeutic Temozolomide (TMZ) widely used to treat glioma tumors is orally given. Here, we tested for the first time the intranasal administration of TMZ in nude mice xenograft models carrying human glioblastoma tumors generated from the human glioma stem-like cells TG16, TG1N and TG20.

Methods: The resistance to TMZ of the different glioma stem-like cells was determined by WST-1 cell proliferation and cell viability assay. Tumour cells were stereotaxically injected intrastriatally and one month after graft, mice were anesthetized using Isofluorane and TMZ was infused into the nostrils three times a week during two weeks with a nano-injector using Hamilton syringe coupled to a cannula. Buried food pellet test was carried out to check the sense of smell. Animals were weighted and surveilled once a week and separated into two cohorts, one for histopathological analysis and the other for Kaplan-Meier survival analysis.

Results: Intranasal administration of TMZ did not induce major adverse effects on the sense of smell of the animals. TMZ administred intranasally delayed tumour growth and significantly extended the lifespan of mice engrafted with TG16 and TG1N cells, which are sensitive in vitro to TMZ. By contrast, TMZ at the dose tested had no effects on the tumors generated by TG20 cells that are resistant to TMZ in vitro.

Conclusion: Our results demonstrate that the intranasal route should be further considered as an option for TMZ delivery into the brain to treat intrastriatal brain tumours. Moreover, it consists of an easy, fast, and cost-less method to gain direct access to the brain.

From the birth of mankind, cancer is known as one of the most notorious and deadly diseases human kinds has ever faced on this earth. Many methods and ways are implemented to eliminate this disease and the number is still on the increasing side. It’s been a couple of decades that the idea of nanotechnology was first introduced, where nanoparticle is part of that. Cerium oxide nanoparticle also known as nanoceria is one of the metal oxide nanoparticles which holds promise to treat cancer effectively. Scientists have found fruitful result ignoring the drawbacks of this particular particle and there are ongoing researches to unlock the full potential of cerium oxide nanoparticle in the case of cancer treatment as well as eliminate its drawbacks.

Introduction: The Abscopal effect refers to radiotherapy-induced tumor regression in lesions distant from a targeted site, and is a rare phenomenon in patients receiving local radiotherapy. This report is the first to describe an Abscopal response in a chemotherapy-naïve non-small cell lung cancer (NSCLC) patient following whole-brain radiotherapy as well as palliative radiotherapy.

Case presentation: A 63-years-old man who was a current-smoker (with 86 pack years) with metastatic NSCLC underwent whole brain radiotherapy (WBRT) plus boost radiotherapy to total dose of 45 Gy in 15 fractions because the metastatic brain tumor with cerebral oedema from the left temporal lobe to the occipital lobe rapidly progressed after the enucleation of the brain tumor. The patient also received palliative radiation (30 Gy in 10 fractions) for the third lumbar vertebral metastasis. The tumor in the left upper lobe of the lung and his mediastinal lymph nodes had regressed in size upon reviewing his follow-up CT results seven weeks post-radiotherapy.

Conclusion: The Abscopal effect in metastatic NSCLC patients can occur after the irradiation of metastatic lesions without chemotherapeutic or immunotherapeutic interventions.

Introduction: Breast cancer is both genetically and histopathologically heterogeneous disease. The biological basis for this heterogeneity is unknown, although there are some distinct phenotype-genotype correlations. Approximately 5% to 10% of breast cancer is hereditary and BRCA1 and BRCA2 genes are responsible for the majority of the hereditary cases of breast cancer. According to the existing literature BRCA1 and BRCA2 associated breast cancer, it has been shown that BRCA associated breast cancers have different clinical, histological and immune-phenotypic features. To validate the effect of BRCA 1 or BRCA 2 germ line mutations on breast cancer aggressiveness and its impact on breast cancer clinical and histological features, we compared the histological, molecular status and clinical variables of 32 breast cancer patients with BRCA gene pathogenic mutations carriers and to the histopathological and molecular characteristics of 50 patients affected with breast cancer in the same age group but with no pathogenic mutations or variants of unknown significant (VUS) in either BRCA1 or BRCA2 genes.

Methods: A retrospective study was conducted to study breast cancer cases that were evaluated at the hereditary breast and ovarian cancer clinic at the national center of cancer care and research (NCCCR) in the State of Qatar from 2013 to 2015. Review of medical records was conducted to determine the clinical characteristics, the molecular results of BRCA testing and the tumor characteristics from the histopathology reports in addition to a new review of the tumor blocks to update the molecular data of those patients.

Results: (82) patients with breast cancer were diagnosed at a young age (50 years of age and younger). (50) patients were BRCA negative and (32) patients were i positive. (22) Patients were found to have BRCA1 pathogenic mutations, (9) patients had BRCA2 pathogenic mutations and (1) patient carried pathogenic mutations in both BRCA1 and BRCA2 genes. Most patients had mutations in the BRCA1 with most mutations being small frame shift deletion or insertion in one or more exons that caused protein truncation. BRCA mutations was detected among women of younger ages. In terms of histopathology, the majority of BRCA associated breast cancers are invasive ductal carcinoma (IDC) detected in 94% with (74%) high nuclear grade 3/3, have a higher number of mitosis and show a high frequency of necrotic areas, and a higher proliferative rate and lymphocytic infiltration. All of these histopathological features point toward a more aggressive tumor type. In terms of immunohistochemical (IHC) tumor markers, triple negative detected in 56.3% accounted for most of the BRCA associated breast cancers. Triple positive accounted for 9.4%, followed by ER PR positive Her2 negative (34.4%) and ER PR negative Her2 positive (0%). Disease staging of all patients with breast cancer is done according to AJCC staging manual. Patients with BRCA pathogenic mutations diagnosed with stage II 60% followed by stage III 26.6% and stage IV14%. Patients with no pathogenic mutations in the BRCA genes also had IDC as being the most common histopathologcal type IDC 58% but also exhibited other type of histopathology such as ductal carcinoma in situ (DCIS) (10%), invasive lobular carcinoma (ILC) (6%), lobular carcinoma in situ (LCI). BRCA negative breast cancers exhibited 2% nuclear grade 3/3 in 36% of cases and high proliferative rate in 31%. Triple negative breast cancers accounted for 17%, triple positive 13%, ER PR positive Her2 negative 44% and ER PR negative Her 2 positive 13%. In terms of disease stage, those with no pathogenic mutations in the BRCA genes mostly had stage I 39% followed by stage II 61%, stag III 29%, and no cases were diagnosed with stage IV.

Conclusion: These results suggest that breast cancers associated with BRCA mutations are more likely to be basal sub-type and exhibits more aggressive behavior, particularly in younger age groups and those patients present with a more advanced stage of disease than those with no pathogenic mutations in the BRCA genes who exhibit a less aggressive disease. We will continue to build our database for better characterization of our hereditary breast cancer cases at a clinical and molecular levels and use this information for future development of targeted anti-cancer agents use.

Objective: Fluorouracil, cisplatin, and taxane are widely used in the standard chemotherapy regimens for esophageal squamous cell carcinoma (ESCC). Although S-1 is expected to demonstrate considerable efficacy for ESCC, there is any clinical data. The purpose of this retrospective study was to evaluate the efficacy and safety of S-1 as salvage chemotherapy for ESCC.

Methods: From 2007 to 2014, fifteen patients with ESCC refractory or refusal to the standard chemotherapy were treated with S-1 as salvage treatment at the Kyoto University Hospital and their clinical records were reviewed retrospectively.

Results: The median age was 70 years old (range: 63-77). A complete response (CR) was achieved in 1 case (7%). A stable disease (SD) and progressive disease (PD) were seen in 9 (60%) and 5 (33%) cases, respectively. After a follow-up duration of 13.9 months, median progression free survival and overall survival was 6.2 and 10.0 months, respectively. One-year survival rate was 33.3%. Toxicities greater than CTCAE grade 3 were observed in 3 of 15 patients (20%). Two patients had grade 3 neutropenia and one patient had grade 3 diarrhea. There was no treatment related death.

Conclusions: S-1 salvage chemotherapy could be expected to be an effective and safe treatment option to improve the prognosis of patients with ESCC refractory to the standard chemotherapy.

Object: Cancer stem cells (CSCs) have recently started attracting attention as targets cancer treatment. Despite many studies, markers of effective CSCs of heterogeneous ovarian carcinoma (OC) that can be directly used for medical treatment have not yet been reported. The aim of this research was to identify a new combination of surface markers for human ovarian CSCs.

Methods: Primary serous adenocarcinomas were obtained from patients with OC. FACS were used to decide cell surface marker to characterize and isolate cancer stem cells from primary human cancer tissues. RT-PCR methods were used for estimating the expression levels of mRNA, and immunohistochemistry confirmed the produce of the stemness relative protein after cell sorting. Xenograft model was used for the ability of tumorogenesis.

Results: We found that the cultured cells strongly expressed stemness genes such as c-myc, oct3/4, sox2, nanog, abcg-2, and bmi-1. They also expressed surface markers such as CD24, SSEA4, CD133, and CD47. The sub-population of CD24+ SSEA4+ double positive cells showed strong expression of Oct-4, and was able to form spheres much more than CD24-SSEA4+ cells, CD24+SSEA4-cells or CD24- SSEA4-double negative cells. Only 5 CD24+SSEA4+ cells formed spheres within 3 weeks. This sub-population formed the highest number of colonies in the soft agar colony assay. The CD24+SSEA4+ cells showed better growth in the presence of cisplatin than the other sub-populations. CD24+SSEA4+ cells were tumorigenic in all scid mice (4/4) within 2 months, with an injection of 100 cells/mouse.

Conclusion: These results suggested that CD24+SSEA4+double positive cells have characteristics similar to that of human ovarian tumor CSCs. It might be possible to develop effective new clinical therapies for human ovarian cancer (OC) using these cells as targets.