Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Il compenso nella neurite vestibolare. [Compensation in vestibular neuronitis]

After a vestibular neuronitis, the majority of patients with functional residual deficit reach a static vestibular compensation. Only in 16% of patients in fact a spontaneous nystagmus after 6 months is detectable. Contrarily vestibular dynamic signs tend to persist probably because mechanisms of adaptation hardly succeed to be effective when we use high velocity stimulus, particularly if the peripheral organ is heavily damaged. Generally patients with a vestibular persistent caloric areflexia show a deficit in vestibule-oculomotor reflex during a rapid rotation of the head or a persistent nystagmus induced by Head Shaking (HSTest). Instead in 50% of patients with residual hyporeflectivity after 6 months we can observe a dynamic compensation. From the analysis of our data, it appears that the caloric test, though considered a gold standard in detection of peripheral vestibular deficit, can supply missleading negative results, even if this is rare. In our survey, in fact, there are patients that present a normal caloric test after 3 and 6 months of deficit, but an HST pathologic

A case of subacute cutaneous lupus erythematosus in a patient with mixed connective tissue disease: successful treatment with plasmapheresis and rituximab.

A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE). Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL) IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE) followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX) (375 mg/m(2) weekly for 4 weeks). Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed

Chemotherapy in female urethral cancer

Urethral cancer is a rare female urogenital tract cancer. There is scarce literature about it, consisting mostly of small-scale retrospective analyses and case reports and no unanimous consensus on standard treatment is available. We report a case of complete clinical response to chemotherapy of primary carcinoma of the female urethra

Assessing the role of low volume disease in endometrial cancer

The role of retroperitoneal staging in endometrial cancer is still unclear. Although the prognostic value of lymphadenectomy has been demonstrated no data support the therapeutic value of nodal dissection. Sentinel node mapping represents an evolution of lymphadenectomy. Sentinel node mapping allows a more accurate identification of low-volume diseases (i.e., micrometastasis and isolated tumor cells) that are not always detectable via conventional histopathological evaluation. Adjuvant therapy might play a role in patients with low-volume disease. However, the presence of isolated tumor cells alone seems to not impact outcomes of endometrioid endometrial cancer patients. Hence, the choice to deliver adjuvant therapies has to be tailored based on uterine factors only. The introduction of molecular and genomic profiling would be useful in selecting appropriate surgical and adjuvant treatments. The molecular-integrated risk profile should be integrated in clinical practice to overcome the need of retroperitoneal staging (in case of non-bulky nodes) in patients at low risk