A Review on the Role of AFAP1-AS1 in the Pathoetiology of Cancer

AFAP1-AS1 is a long non-coding RNA which partakes in the pathoetiology of several cancers. The sense protein coding gene from this locus partakes in the regulation of cytophagy, cell motility, invasive characteristics of cells and metastatic ability. In addition to acting in concert with AFAP1, AFAP1-AS1 can sequester a number of cancer-related miRNAs, thus affecting activity of signaling pathways involved in cancer progression. Most of animal studies have confirmed that AFAP1-AS1 silencing can reduce tumor volume and invasive behavior of tumor cells in the xenograft models. Moreover, statistical analyses in the human subjects have shown strong correlation between expression levels of this lncRNA and clinical outcomes. In the present work, we review the impact of AFAP1-AS1 in the carcinogenesis.

Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential

Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl− channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.

Carbon quantum dot–NO photoreleaser nanohybrids for two-photon phototherapy of hypoxic tumors

Carbon quantum dots conjugated with a NO photodonor reduce tumor volume in mice bearing human xenograft BXPc-3 pancreatic tumors upon two-photon excitation with NIR light.

Neoadjuvant Treatment in Rectal Cancer: Actual Status

Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas.

TREATMENT OF CHORDOMAS WITH CYBERKNIFE

OBJECTIVE To determine the efficacy and safety of chordoma treatment with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (CK/SRS). METHODS Eighteen patients with chordoma were treated with CK/SRS as a primary adjuvant (17 patients) or the only treatment (1 patient). The series included 24 lesions (28 treatments). The median age of the patients was 60 years (range, 24–85 years). Forty-four percent of the tumors were located in the mobile spine, 39% inside the cranium, and 17% in the sacral region. The male-to-female ratio was 1:1. The mean tumor volume was 128.0 mL (range, 12.0–457.3 mL), and the median dose of 35 Gy (range, 24.0–40.0 Gy) was delivered in 5 sessions. The median follow-up period was 46 months (range, 7–65 months). RESULTS There were 3 significant complications in patients with previous irradiation, including infection in the surgical/radiation site (2 patients) and decreased vision (1 patient). Improvement in pain and quality of life did not reach statistical significance (α = 0.05). Seven patients experienced recurrence at a median of 10 months (range, 5–38 months), and 4 patients with disseminated disease died 7 to 48 months after therapy. Two patients had a partial response, whereas 9 others had stable disease. The local control rate at 65 months was 59.1%, with an overall survival of 74.3% and disease-specific survival of 88.9%. We estimated an α/β ratio of 2.45 for chordomas, which supports hypofractionation. CONCLUSION The CK/SRS safety and efficacy profile compares favorably with those of other treatment delivery systems. CK/SRS appears to reduce tumor volume, given an adequate dose. The authors recommend treatment with 40 Gy in 5 sessions to the clinical treatment volume, which includes the gross tumor volume and at least a 1-cm margin.

SURGICAL TREATMENT OF GIANT PITUITARY ADENOMAS

OBJECTIVE Giant pituitary adenomas, defined as those measuring at least 4 cm in maximum diameter, are a therapeutic challenge. We report our experience in a large, consecutive series of patients with giant adenomas. METHODS Between 1990 and 2004, 95 patients with a giant pituitary adenomas underwent surgery at our department. Nonfunctioning pituitary adenoma was the most frequent type (n = 70; 73.7%), whereas hormone-secreting adenomas numbered only 25 (26.3%). The mean age at the time of surgery (±standard error of the mean) was 48.4 ± 1.5 years; there were 66 men (69.5%) and 29 women (20.5%). RESULTS In total, 111 surgical procedures were performed. Of these, 85 approaches (76.6%) were transsphenoidal and 26 (23.4%) were transcranial. Visual improvement occurred in 59 of the 79 patients with preoperative defect who could be evaluated after surgery (74.7%). Radical tumor excision was obtained in 14 patients (14.7%). Adjuvant medical and radiation therapies led to 74.5% (95% confidence interval, 62.7–86.4%) control of tumor growth at 5 years. This was not different in patients with nonfunctioning pituitary adenomas compared with patients with hormone-secreting tumors. In the subgroup of patients with nonfunctioning pituitary adenomas, radiation therapy had a protective role against tumor growth (P < 0.01). CONCLUSION Maximal surgical removal of giant adenomas through the transsphenoidal or transcranial approach, or both, aimed to relieve compression of the optic pathway and reduce tumor volume as much as possible, offers the best chances to control the tumor when followed with adjuvant medical and radiation therapies.