がんの科学と治療

TP53, encoding p53, is one of the most famous tumor suppressor genes. The majority of human cancers demonstrate the inactivation of the p53 pathway. Mutant p53 not only, no longer, functions as a tumor suppressor but can also exert tumor-promoting effects. The basic function of p53 is to respond to cellular stress. We here in this review article discusses about the recent advances in p53 research, mainly focusing on apoptosis and therapy for human cancer. Hence, this review aims to update the current related articles and provide a further understanding about such molecular changes relevant to trigger imbalances in the regulation of apoptosis in cancer.

Kaposi’s sarcoma (KS) is an opportunistic tumor proliferation Multicenter cells derived from lymphatic endothelium, infected with human herpes virus 8 (HHV-8). It is a heterogeneous disease distribution, which can be linked to poor prognosis. HHV-8 infection and immunosuppression are essential to its development [1,2]. These two elements are constant in the four clinical-epidemiological forms of KS: classical form, originally described by Moritz Kaposi typically affecting elderly men of Mediterranean, the endemic presence in Southern Africa, the epidemic form in patients infected HIV, and, finally, the MK complicating iatrogenic immunosuppression, particularly after organ transplantation [3]. This work exposes the real place of chemotherapy in adult patients with Kaposi sarcoma, among the available therapeutic means.

Melanoma is the most serious form of skin cancer. The quest for melanoma diagnostic biomarkers is paramount since early detection of melanoma and surgical excision represent the only effective treatment of this capricious disease. Our recent study tested the hypothesis that melanoma forms a unique volatile signature that is different than control, healthy tissue. Here, we are reporting a case study, the analysis of the volatile metabolic signature of a malignant melanoma using matched, non-neoplastic skin tissue from the same patient as a control. This is a significant improvement in the methodology, since it is well known that diet, skin type, genetic background, age, sex and environment all contribute to individual variation in the skin volatile signature. In the present study, we have identified 32 volatile compounds; 9 volatile compounds were increased in melanoma when compared to normal skin and 23 volatile compounds were detected only in melanoma and not in normal skin. Out of these 32 compounds, 10 have been reported previously by our group, thus confirming our results and adding additional confidence in our untargeted metabolomics approach for detection of melanoma biomarkers.

Accumulating evidence shows that the central nervous system (CNS) regulates the activity of the immune system. Concerning the role of immune system in cancer, psychosocial influences on immune function provide a mechanism of association between psychosocial factors (like interpersonal aggression) and cancer prognosis. Social conflicts between males, involving high aggression stress and threat (psychosocial conflicts) produce both an allostatic state and allostatic load. The costs for aggressors (Hawks) and victims (losers) tested under semi laboratory conditions are quite different. Testosterone does not cause aggression, only exaggerates the pre-existing pattern and response to environmental triggers of aggression. The individual’s personality type (authoritarian Hawk or Dove) has major impact on psychoneuroimmune mechanisms linking aggression stress through inflammation to cancer. Due to the latest connotations we propose this personality phenomenon label as “the Strauss-Kahn syndrome”.

Objective: Interventional therapy for advanced hepatocellular carcinoma (HCC) is still controversial. This retrospective study was to evaluate the efficacy of transcatheter arterial infusion (TAI) alone or combined with transcatheter arterial chemoembolization (TACE) on advanced HCC. Methods: The study population consisted of 132 advanced HCC patients with Child-pugh A/B. Tumor in all patients was involved with main trunk of portal vein and/or inferior vena cava, or local lymph node metastasis, or distant metastasis. TAI alone or combined with TACE were performed in 65 patients with advanced HCC (interventional treatment group), 67 patients were treated with traditional Chinese herbal drug (Chinese herb group). The prime end point was overall survival (OS), and prognostic factors were analysed. Results: The median OS was 205 days [95% confidence interval (CI), 155-255 days] in interventional treatment group and 127 days (95% CI, 70-184 days) in Chinese herb group (P <0.05). The 6-month, 1-year, and 2-year OS rates were 58.9%, 29.1%, 7.7% in interventional treatment group, and 33.3%, 12.3%, 1.8% in Chinese herb group. The portal vein thrombosis, ECOG performance status were independent prognostic factors for OS. Conclusion: Interventional treatment could greatly prolong the OS of advanced HCC patients.

Background: Fractionated external beam radiotherapy followed by intracavitary brachytherapy is the mainstay of treatment in cervical cancer. Due to long radiotherapy course, patients in developing countries default effective radiotherapy. Treatment break or discontinuance leads to treatment failure. Continuous hyperfractionated accelerated radiotherapy (CHART) is an altered fractionation scheme used to reduce overall treatment time, overcome tumor repopulation thus could be an option in cervical carcinoma. Methods: Twenty-five histopathological documented locally advanced cervical carcinoma (FIGO stage IB2- IVA) were treated with 42Gy/30fractions external radiotherapy over 10-day period at an inter-fraction interval of 6 hours using CHART technique. Following CHART, patients were subjected to high dose rate brachytherapy to a dose schedule of 9Gyx2 at weekly interval. The response to above radiotherapy protocol and morbidity pattern was evaluated. Results: All patients completed planned CHART external radiotherapy. The median follow-up was 32-months with a pelvic control rate of 68% and 24-month overall survival was 72%. The most common acute toxicity in CHART technique was fatigue (64%) and diarrhea (52%), the late effects being rectal bleeding (2-cases), subcutaneous fibrosis (1-case), spinal pain (1-case). Conclusion: CHART technique is an effective and well tolerated technique in locally advanced cervical cancer at a cost of manageable fatigue and diarrhea. Further investigation involving large number of patients is warranted to evaluate this technique.

Background: Tissue microarrays (TMAs) have been commonly utilized in translational research to rapidly screen numerous biomarkers in large samples. One major concern has been the adequate assessment of biomarkers affected by within-tumor heterogeneity and by molecular targets. Methods: Our study was designed to answer a fundamental question: How do researchers define the optimal cores to sample when designing a TMA study to minimize sampling bias and core artifact? We compared the staining results from a full-section tissue slide to the virtual TMA and from the actual TMA to the virtual TMA. Results: Three cores were demonstrated as optimal for markers such as TTF-1 and p53, but no optimal core number could be determined for markers such as Ki-67 due to the poor TMA representation of the entire tissue. Conclusion: We propose that before using TMAs to analyze large samples, particularly with significant withinsample heterogeneity, a preliminary investigation using a virtual TMA could help decide target markers to be tested for valid and valued results.