がんの科学と治療

Melanoma is a malignancy of melanocytes of cutaneous, uveal or mucosal origins. This review discusses advances in biology and new approaches in staging and advanced disease therapy. The role of UVA light in dark reactions generating dioxetane products and cyclobutane pyrimidine dimers in melanoma genesis is detailed. Utility of screening programs and prevention with enhanced UVA blockers is included. Different staging algorithms for cutaneous, uveal and mucosal melanomas are described. Advances in adjuvant radiotherapy and immunotherapy are noted. Stereotactic radiotherapy for brain metastases and metastasectomy for oligometastatic disease has impacted the natural history of this disease. While combined BRAF and MEK inhibition for BRAF mutant melanoma patients have produced durable remissions, relapse is frequent and due to multiple genetic mechanisms. Immunotherapy with anti-CTLA4 and anti-PD1 immune checkpoint blockers also yields long-term responses, but there remains many patients unresponsive to immune checkpoint blockade or whom develop resistance. Host and tumor-specific resistance mechanisms are explored. Some new areas of melanoma research include nanoparticle fluorescence surgical imaging for regional and metastatic disease, tumor gene expression profiling to predict BRAF inhibitor resistance, combination of ion channel blocker with MEK inhibitor for wild-type BRAF metastatic melanoma, establishment of the innate immune signalling pathway for stereotactic radiotherapy of melanoma, and testing of IDO inhibitors with anti-PD1 inhibitors in metastatic melanoma.

Background: Tumors of the parapharyngeal space (PPS) are rare and account for only 0.5% of head and neck neoplasms. Approximately 80% of these tumors are benign lesions, yet they represent a formidable diagnostic and treatment challenge. They are difficult to diagnose because they have few symptoms, therefore, CT and MRI are essential to delineate the tumor extent, intracranial involvement and relationship to the adjacent vital structures. Case presentation: We report the case of a 36-year-old male who presented with the sudden onset of a pharyngeal cavity mass. CT head and neck scan and MRI showed a left paraphayngeal mass occupying the prestyloid parapharyngeal space extending to poststyloid. Transorally biopsy revealed a well differenced squamous cell carcinoma. A FDG PET/CT was performed and revealed outside the known tumor, vertebral metastasis of the cervical and thoracic spine, a right collarbone metastasis and pulmonary nodules. It was decided to manage this metastatic squamous cell carcinoma with chemotherapy. Conclusion: Parapharyngeal squamous cell carcinomas are extremely rare. Imaging helps in planning the surgical procedure. Radionuclide imaging is complimentary to radiological imaging and provides specific information about the tumor’s functional and molecular characteristics. This case of squamous cell carcinoma presents several unusual features: the scarcity of squamous cell carcinoma in the paraphayngeal space and faraway metastasis in this type of tumor. Moreover the role of FDG PET/CT have been exceptionally described in the literature.

To identify non-pharmacological strategies in the control of pain and dyspnea, in patient with oncological disease, in acute care. The gold standard to an adequate symptom control is a systematized assessment. Non-pharmacological measures: psycho-emotional support, hypnosis, counseling/ training/ instruction, therapeutic adherence, music therapy, massage, relaxation techniques, telephone support, functional and respiratory re-education increase health gains. The control of oncologic pain and dyspnea require a comprehensive and multimodal approach.

Background: Cisplatin is widely used as radio sensitizer in head and neck cancer (HNC) and cervical cancer. We conducted this prospective study to evaluate cisplatin induced toxicity as once-weekly regimen in HNC and cervical cancer during concurrent chemoradiotherapy (CCRT) to optimize its administration. Patients and methods: From 01 January 2015 to 11 May 2015, a data of all eligible patients treated by chemoradiation regimens containing a low dose of cisplatin were collected at the Department of radiotherapy in National Institute of Oncology in Morocco. Cisplatin was used weekly at 40 mg/m2 with adequate hydration and premedication in all patients. A complete blood count and renal function tests were done prior to each cycle of chemotherapy to evaluate toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Results: A total of 96 patients were eligible for the analysis. Mean age, PS, initial weight, enteral nutrition, cisplatin mean dose, use of oral Ondansetron and baseline serum tests did not differ significantly among the types of malignancy. However, weight loss was significantly noted among HNC group compared to cervical cancer patients with 6.06 ± 2.92 kg and 0.02 ± 0.13 kg respectively. Toxicity was observed only in 16 (20%) patients after the 4th week of treatment especially among HNC group. The neutropenia and thrombocytopenia were significantly greater for patients of HNC. However, we did not observe any renal toxicity, thrombocytopenia and ≥ grade 3 neutropenia toxicity in cervical cancer group. In multivariated analysis, only a subtype of HNC (OR, 1233; 95% CI, 16-95 103; P=0.001) and grade 2 emetogenicity (OR, 34.8; 95% CI, 2.1-583; P=0.014) were significantly associated with an increased risk for cisplatin toxicity. Whereas, less than 4 weekly cisplatin treatment (OR, 0.4; 95% CI, 0.1-0.9; P=0.046) was associated with a significantly reduced risk. Conclusion: Our data have revealed that individuals with HNC were at a significantly higher risk for cisplatininduced toxicity during CCRT and suggest that the once-weekly smaller dose of cisplatin regimen and conventional prophylactic procedures of administration might be effective for protection against the renal toxicity of cisplatin.

5-Fluorouracil (5-FU) has a wide anticancer activity versus several types of solid tumors. The activity of 5-FU can be improved and its toxicity can be diminished by enhancing the relative specific accumulation in the tumor regions. The aim of this work was to develop Eudragit RS100 based 5-FU microsponges (MS) for treatment of colon cancer. Oil in oil emulsion solvent diffusion method was used for the preparation of 5-FU sustained release Eudragit RS100 MS. MS were characterized for their encapsulation efficiency, production yield, drug polymer interaction and drug release profiles. Shape, surface morphology visualized by scanning electron microscope (SEM) and particle size of MS was investigated using laser light scattering technique and. Eventually, HCT 116 and CACO2 cell lines were used for determination of cell viability by MTT assay. The results showed that all prepared MS were spherical in shape with several pores on their surfaces. The production yield was in (62.76% ±1.06% and 93.80% ± 1.75%), encapsulation efficiency was in (71.80% ± 1.62% and 101.3% ± 2.60%) and particle size was in ( 53.11 μm ± 41.03 nm and 118.12 μm ± 48.21 nm). Fourier transform infrared revealed that there is no chemical interaction between 5-FU and Eudragit RS100. MS loaded 5-FU was more effective than 5-FU itself as shown by cell viability assay. The results demonstrated that 5-FU with Eudragit RS100 was successfully formulated as sustained release manner and could be a substitution delivery method of 5-FU for oral anticancer treatment.

Background: Arsenic trioxide (ATO) is highly effective in the treatment of patients with acute promyelocytic leukemia (APL). It is a chemotherapeutic agent that has been shown to induce apoptosis in several tumor cell lines. However, research into its effects on colon carcinoma cells is still very limited. We previously reported that ATO is cytotoxic and causes DNA damage in HT-29 human colorectal adenocarcinoma cells. In the present study, we further evaluated its effect on oxidative stress (OS), and examined its apoptotic mechanisms of action on HT-29 cells. Methods: OS was assessed by spectrophotometric measurements of MDA levels while cell cycle analysis was evaluated by flow cytometry to determine whether ATO induces cell cycle arrest. Its effect on early apoptosis was also evaluated by flow cytometry using Annexin V-FITC/PI staining. Fluorescence microscopy was used to detect the morphological changes, and Western blotting was carried out to determine the expression of apoptosis-related proteins. Results: The lipid peroxidation assay revealed a dose-dependent increase in MDA production. DAPI staining showed morphological changes in the cell’s nucleus due to apoptosis. Cell cycle analysis and Annexin V-FITC assay also demonstrated a dose-dependent effect of ATO in the accumulation of cells at the sub G1 phase, and the percentages of Annexin V-positive cells, respectively. Western blot data showed that ATO upregulated the expression of caspase 3, Bax, and cytochrome C, and down-regulated the expression of Bcl-2. Conclusion: Taken together, our findings indicate that ATO induces OS and cytotoxicity in HT-29 cells through the mitochondria mediated intrinsic pathway of apoptosis.