Skin toxicity in a patient with ovarian cancer treated with pegylated liposomal doxorubicin: A case report and review of the literature.

Pegylated liposomal doxorubicin (PLD) is a form of doxorubicin enclosed in pegylated liposomes. In contrast to conventional doxorubicin, PLD is characterized by a lower incidence of cardiotoxicity and myelosuppression. However, it induces specific mucocutaneous side effects, particularly palmar-plantar erythrodysesthesia (PPE). Other dermal manifestations, such as intertrigo-like dermatitis, diffuse follicular rash, melanotic macules, maculopapular rash or recall phenomenon are less common. Mechanisms that lead to skin toxicity remain unclear, however, certain reports indicate that drug excretion in sweat, host-vs.-altered-host reactions and local mechanical microtrauma play an important role in the development of cutaneous disorders. Effective preventive and curative management has not yet been established. The current study reports a case of a 55-year-old patient with advanced ovarian cancer who developed an uncommon diffuse maculopapular rash and severe PPE during treatment with PLD. Complete regression of the skin disorder was observed after 4 weeks. At present, palliative chemotherapy provides the opportunity to prolong life and alleviate disease symptoms, nonetheless it produces a number of adverse effects. Dermal complications may affect patient quality of life and cause therapy interruption. In the light of widespread use of PLD, skin toxicity associated with this drug creates a major problem.

CA-SSR1 Polymorphism in Intron 1 of the EGFR Gene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab.

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) inhibitors are not equally effective in all cancer patients. One potential clinical factor that could help in selecting patients who may benefit from treatment with cetuximab is acneiform rash, which correlates with the clinical response to EGFR inhibitors. Some previous studies have suggested that the tendency to develop rash may depend on polymorphisms in the EGFR gene. In this investigation, the association of degree of CA dinucleotide polymorphism with skin rash and cetuximab therapy outcome was examined. METHODS: The study included 60 patients treated with cetuximab. For each patient, the severity of acneiform rash was assessed, and the type of polymorphism was determined by genotyping. Associations between genotypes, the acneiform rash, and response to treatment were determined by using the chi-square test and Spearman's rank correlation. The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions. RESULTS: A correlation was found between body surface area covered by rash and the sum of the two allele repetitions (p=0.030). No statistically significant relationship between genotype and response to treatment was observed. However, in patients who have had partial remission, we noticed a higher incidence of polymorphism, with less CA dinucleotide repetitions and early onset of rash. CONCLUSION: A correlation between genotype and severity of rash was observed. That is, the severity of rash decreased with an increased number of CA repetitions.

Secondary cancer in a survivor of Hodgkin's lymphoma: A case report and review of the literature.

Hodgkin's lymphoma (HL) is one of the most curable malignant diseases in adults. However, HL patients have a higher risk of developing second malignancies compared with the general population. The population of adult cancer survivors is growing, thus, the long-term effects of cancer treatment, including secondary cancer development, have become an increasingly important concern in the field of oncology. The current study presents the case of a female HL survivor who developed two secondary malignancies within 29 years of follow-up. Furthermore, a review of the literature was conducted, which focused on secondary breast and gastrointestinal cancers in HL survivors.

Malignant acanthosis nigricans associated with prostate cancer: a case report.

BACKGROUND: Acanthosis nigricans is characterized by hyperpigmentation and hyperkeratosis of the skin or mucous membranes. Its malignant form is associated with internal neoplasms, especially gastric adenocarcinoma (55-61%). Coexistence with prostate cancer is uncommon. In the paraneoplastic type of this dermatosis, the skin and mucous lesions are characteristically of more sudden onset and more severe than those in the benign form. The efficacy of various treatment strategies remains disappointing. CASE PRESENTATION: We here report a case of 66-year-old Caucasian patient with metastatic prostate cancer and a mild form of acanthosis nigricans that preceded the diagnosis of malignancy and resolved with chemotherapy in parallel with the prostate cancer. The dermatosis recurred when the prostate cancer progressed. CONCLUSION: Concurrent acanthosis nigricans and prostate cancer is rare, and few such cases have been reported. Anti-tumor therapy occasionally results in regression of this dermatosis. Underlying malignant disease should be suspected in individuals with elderly-onset of acanthosis nigricans.

[PARP inhibitors--theoretical basis and clinical application]. / Inhibitory PARP--podstawy teoretyczne i zastosowanie kliniczne.

Poly-ADP-ribose polymerases (PARP) are involved in a number of processes that are vital for every living cell. Once activated by the presence of DNA damage they trigger poly-ADP-ribosylation of various proteins which are crucial for DNA repair, preserving of genom integrity, regulation of transcription, proliferation and apoptosis. PARP1, which is the best known enzyme of PARP protein family, plays a role in single-strand breaks (SSB) repair. Decrease of its activity results in accumulation of single strand DNA breaks (SSB) which leads as a consequence to double-strand breaks (DSBs). This disorder is particularly harmful to cells with deficiency of BRCA1/2 protein which is involved in repair of DNA double-strand breaks. This phenomenon is an example of "synthetic lethality" concept and contributes to research on application of PARP inhibitors in treatment of cancers associated with BRCA1/2 protein defect (breast or ovarian cancer). Noticed synergism between PARP inhibitors and genotoxic chemotherapy or radiotherapy determined another direction of research on application of these medicaments. After promising results of phase I and II trials with most commonly investigated PARP inhibitors--iniparib and olaparib--which recruited patients with triple negative breast cancer and ovarian cancer, further studies started. This paper presents theoretical basis of PARP inhibitors action as well as critical review of most important clinical trials of these medicaments.

[Transmembrane transporters ABCC - structure, function and role in multidrug resistance of cancer cells]. / Transportery blonowe ABCC ­ budowa, funkcja i znaczenie w mechanizmach wytwarzania opornosci wielolekowej w komórkach nowotworów zlosliwych.

Resistance to cytotoxic drugs is a significant problem of systemic treatment of cancers. Apart from drug inactivation, changes in target enzymes and proteins, increased DNA repair and suppression of apoptosis, an important mechanism of resistance is an active drug efflux from cancer cells. Drug efflux across the cell membrane is caused by transport proteins such as ABC proteins (ATP-binding cassette). This review focuses on the ABCC protein subfamily, whose members are responsible for multidrug cross-resistance of cancer cells to cytotoxic agents. The authors discuss the structure of ABCC proteins, their physiological function and diseases provoked by mutations of respective genes, their expression in many different malignancies and its connection with resistance to anticancer drugs, as well as methods of reversion of such resistance.

[High risk of atherosclerosis in men aged 20-39 from Lodz agglomeration]. / Wysokie ryzyko wystapienia miazdzycy u mezczyzn w wieku 20-39 lat z aglomeracji lódzkiej.

THE AIM OF THE STUDY: To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of the highest in Poland fatality rate of circulatory system diseases. MATERIAL AND METHODS: Anamnestic data on actual diseases, smoking, alcohol drinking and physical activity were achieved from 80 men, volunteers aged 20-39 years. Body weight and height, waist and hip circumference and arterial blood pressure were measured. Blood levels of lipids: total cholesterol (TCh), its fractions LDL, and HDL (LDL-Ch, HDL-Ch) ,and triglicerydes (TG), glucose, albumins, sex hormone binding globulin (SHBG), FSH, LH, total testosterone, dehydroepiandrosterone sulphate (DHEA-S) and estradiol were determined. Calculated were body mass index (BMI), waist to hip ratio (WHR), free testosterone index (FTI), free and bioactive testosterone. RESULTS: At least 3 atherosclerosis risk factors were simultaneously found in 33.7% of men, of which 22.7% were 20-29-year-old and 47.2% 30-39-year-old subjects. Elevated values of TG were found in 16.2% of men, TCh in 13.7%, LDL-Ch in 7.5% and decreased values of HDL-Ch in 6.2%. Positive significant correlations were found between WHR and TCh (R = 0.39; p = 0.01), LDL-Ch (R = 0.38; p = 0.02), TG (R = 0.41; p = 0.009). WHR negatively correlated with HDL-Ch (R = -0.31; p = 0.04). 50% of men had the excessive body weight. Obese men had abdominal type of obesity in 90%. As many as 62% of subjects had excessive systolic and 21% excessive diastolic arterial blood pressure. Blood pressure positively correlated with body weight (R = 0.51; p < 0.001), BMI (R = 0.51; p < 0.001), waist circumference (R = 0.55; p < 0.001) and WHR (R = 0.44; p < 0.001). In the whole group 35% of subjects led sitting life style and did not report any other physical activity. 57.5% of men were present or past smokers. 44% of men consumed alcohol everyday or almost everyday. FTI diminished with the advancing age, what was connected with the increase in SHBG blood concentration. There were no changes in total, free or bioactive testosterone, or LH and FSH concentrations with the age. Correlations between androgens and lipid profiles were not found. Estradiol blood levels negatively correlated with TG (R = -0.35; p = 0.03) and was significantly lower in 30-39-year-old men than in younger (20-29). CONCLUSION: The results indicate considerably higher incidence of atherosclerosis risk factors in young men, citizens of Lodz agglomeration, than it was found before for other regions of Poland. This phenomenon increases with the advancing age already between 20 and 39 years. Implementation of intensive prophylactic actions may prevent it.