We have developed a novel approach for detection of cancer based on biochemical analysis of peripheral blood plasma using Fourier transform infrared spectroscopy. This approach has proven to be quick, safe, minimal invasive, and effective. Our approach recognizes any signs of solid tumor presence, regardless of location in the body or cancer type by measuring a spectrum that gives information regarding the total molecular composition and structure of the peripheral blood samples. The analysis includes clinically relevant preprocessing and feature extraction with principal component analysis, and uses Fisher's linear discriminant analysis to classify between cancer patients and healthy controls. We evaluated our method with leave-one-out cross validation and were able to establish sensitivity of 93.33%, specificity of 87.8%, and overall accuracy of 90.7%. Using our method for cancer detection should result in fewer unnecessary invasive procedures and yield fast detection of solid tumors.

Leukemia is one of the most common cancers in patients of reproductive age. It is well known that chemotherapy, used as anti-cancer therapy, adversely affects male fertility. Moreover, the negative effect of leukemia on sperm quality, even before chemotherapy treatment, has been reported. However, the mechanisms behind this disease’s effect on sperm quality remains unknown. In this study, we examine the direct effect of leukemia and chemotherapy alone and in combination on sperm parameters and male fertility. For this, we developed an acute myeloid leukemia (AML) mouse model (mice were treated with AML cells C1498 and developed leukemia); these mice then received cytarabine chemotherapy. Our findings reveal a significant reduction in sperm concentration and motility and a significant increase in abnormal morphology and spontaneous acrosome reaction of the sperm following AML and chemotherapy treatment, alone and in combination. We also found a reduction in male fertility and the number of delivered offspring. Our results support previous findings that AML impairs sperm parameters and show for the first time that AML increases spontaneous acrosome reaction and decreases male fertility capacity and number of offspring.

Study question How do AML and cytarabine affect the development of spermatogenesis, germ cell microenvironment and testicular inflammatory factors at the adult age of immature-treated mice? Summary answer AML and cytarabine significantly damaged the normal histology of the seminiferous tubules and impaired different stages of spermatogenesis, testicular growth/inflammatory factor in the adult age. What is known already The effect of different types of cancers on male fertility was reported. AML constitutes around 20% of the diagnosed childhood leukemia. Cytarabine is used as anti-AML treatment. Cytarabine is involved in reduction of testes growth and induces testicular atrophy in adults. In adult AML patients, it was shown that AML affects semen parameters even before chemotherapy treatment. Furthermore, a significant reduction in semen quality of thawed cryopreserved semen from leukemia patients compared to control patients was reported. However, the effect of AML and cytarabine before puberty on the development of spermatogenesis in adult age was not yet reported. Study design, size, duration Two-week-old males C57/BLACK mice were used. 1. Control group – injected with saline. 2. AML group – injected (intraperitoneal; i.p) with 3x104 AML cells/100 ml (murine C-1498 AML cell line). 3. Cytarabine group - three injections of cytarabine (140 mg/kg/100 ml) were performed every 12 hours. 4. AML+cytarabine group – cytarabine was i.p injected 24 hours after AML injection (injections were performed every 12 hours 3 times). Mice were sacrificed 1,2,3,4,5 weeks after AML injection. Participants/materials, setting, methods Testes were removed, weighted and fixed in Bouin’s solution for histological evaluation, or kept at -70°C for RNA extraction. The presence of premeiotic (SALL4, PLZF), meiotic (CREM-1) and postmeiotic (ACROSIN) cells were examined by immunofluorescence staining analysis and/or RNA expression by qPCR analysis. Main results and the role of chance We have successfully developed a system of AML in immature mice by i.p injection of C1498 cells. Cytarabine prolonged life of AML-treated mice from 2.5 weeks to 4 weeks. AML had no effect on both body and testicular weight. However, cytarabine significantly reduced testicular weight (around 50% of the control in the first 3 weeks after treatment, and around 30% of the control from 3-4.5 weeks after treatment; p < 0.001). One and/or 2 weeks after the treatment showed that both AML and cytarabine alone or in combination significantly decreased seminiferous tubules normal histology compared to control, (30%, 20%, 10% respectively) (p < 0.001). Cytarabine, but not AML significantly increased the expression of PLZF and SALL4 after 2 weeks compared to control (p < 0.001). However, each treatment significantly increased the percentages of seminiferous tubules with apoptotic cells compared to control (p < 0.05). AML or cytarabine significantly decreased the percentages of tubules with meiotic and postmeiotic markers compared to control (p < 0.05). Also, AML or cytarabine significantly decreased the testicular protein levels of GDNF, CSF-1 (p < 0.01) but did not affect LIF compared to control. Furthermore, AML or cytarabine significantly decreased the protein levels of IL-10. However, AML significantly increased IL-6 when cytarabine increased it compared to control (p < 0.01). Limitations, reasons for caution Animal model of leukemia may behave different from human model. Wider implications of the findings We successfully developed AML disease in immature mice, and demonstrated its impairment the normal histology of the seminiferous tubules and spermatogenesis in the adult age. We showed that AML and cytarabine affect testicular microenvironmental and inflammatory factors. Our results may assist in development future therapeutic strategies for male fertility preservation. Trial registration number NON