A basic principle of cell physiology is that chromosomes condense during mitosis. However, condensation can be uncoupled from mitotic events under certain circumstances. This phenomenon is known as "premature chromosome condensation (PCC)." PCC provides insights in the mechanisms of chromosome condensation, thus helping clarifying the key molecular events leading to the mitosis. Besides, PCC has proved to be an useful tool for analyzing chromosomes in interphase. For example, using PCC we can visualize genetic damage shortly after the exposure to clastogenic agents. More than 30 years ago, the first report of PCC in interphase cells fused to mitotic cells using Sendai virus was described (virus-mediated PCC). The method paved the way to a great number of fundamental discoveries in cytogenetics, radiation biology, and related fields, but it has been hampered by technical difficulties. The novel drug-induced PCC method was introduced about 10 years ago. While fusion-induced PCC exploits the action of external maturation/mitosis promoting factor (MPF), migrating from the inducer mitotic cell to the interphase recipient, drug-induced PCC exploits protein phosphatase inhibitors, which can activate endogenous intracellular MPF. This method is much simpler than fusion-induced PCC, and has already proven useful in different fields.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.20720

Chromosome condensation outside of mitosis: mechanisms and new tools

The combination of radiotherapy and immunotherapy is one of the most promising strategies for cancer treatment. Recent clinical results support the pre-clinical experiments pointing to a benefit for the combined treatment in metastatic patients. Charged particle therapy (using protons or heavier ions) is considered one of the most advanced radiotherapy techniques, but its cost remains higher than conventional X-ray therapy. The most important question to be addressed to justify a more widespread use of particle therapy is whether they can be more effective than X-rays in combination with immunotherapy. Protons and heavy ions have physical advantages compared to X-rays that lead to a reduced damage to the immune cells, that are required for an effective immune response. Moreover, densely ionizing radiation may have biological advantages, due to different cell death pathways and release of cytokine mediators of inflammation. We will discuss results in esophageal cancer patients showing that charged particles can reduce the damage to blood lymphocytes compared to X-rays, and preliminary in vitro studies pointing to an increased release of immune-stimulating cytokines after heavy ion exposure. Pre-clinical and clinical studies are ongoing to test these hypotheses.

https://www.birpublications.org/doi/pdf/10.1259/bjr.20190224

Harnessing radiation to improve immunotherapy: better with particles?

Introduction
This pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery.

https://link.springer.com/content/pdf/10.1186%2F1471-2407-12-251.pdf

Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer

Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions.

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter bu...

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

Purpose To measure chromosomal aberrations in blood lymphocytes from breast cancer patients treated with radiotherapy after quadrantectomy or tumorectomy. Methods and materials Twenty-two breast cancer patients treated with breast-conserving surgery and radiation were evaluated. Adjuvant chemotherapy was also given to 9 patients. Blood samples were obtained before radiotherapy, after about one-half of the fractions, and at the end of the treatment of the whole breast (50 Gy). Chromosome aberrations in peripheral blood lymphocytes were measured using chemical-induced premature chromosome condensation combined with fluorescence in situ hybridization. Results Radiation treatment produced a significant increase in the yield of chromosomal aberrations. A large interindividual variability was observed. The variability was not related to field size, previous chemotherapy, or treatment morbidity. Chromosome aberrations in lymphocytes at the end of the treatment were significantly higher in the group of patients with no lymph nodes surgically removed before the treatment than in the group of patients with more than 10 lymph nodes removed. Conclusions The number of lymph nodes within the radiation field is an important factor affecting the yield of radiation-induced chromosomal aberrations in breast cancer patients.

Lymph nodes in the irradiated field influence the yield of radiation-induced chromosomal aberrations in lymphocytes from breast cancer patients.

Primary non-Hodgkin's lymphoma of the lacrimal sac is an extremely rare presentation of orbital localization of lymphoma. We present a 45-year-old male patient with primary NHL of the lacrimal sac, stage IE, who was treated with surgery and radiotherapy. Fourteen months after the end of radiotherapy the patient is free of disease and does not show any treatment-related toxicity.

Gustavo Canale Cama

Papers

Lymph nodes in the irradiated field influence the yield of radiation-induced chromosomal aberrations in lymphocytes from breast cancer patients.

Primary non-Hodgkin's lymphoma of the lacrimal sac: a case report.