Emerging role of the pentose phosphate pathway in hepatocellular carcinoma

In recent years, there has been a revival of interest in metabolic changes of cancer cells as it has been noticed that malignant transformation and metabolic reprogramming are closely intertwined. The pentose phosphate pathway (PPP) is one of the fundamental components of cellular metabolism crucial for cancer cells. This review will discuss recent findings regarding the involvement of PPP enzymes in several types of cancer, with a focus on hepatocellular carcinoma (HCC). We will pay considerable attention to the involvement of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Subsequently, we discuss the inhibition of the PPP as a potential therapeutic strategy against cancer, in particular, HCC

Prospects for primary and secondary prevention of cervical adenocarcinoma

This thesis comprises a portfolio of reports examining various aspects of the aetiology, diagnosis, treatment and pathogenesis of Cervical Intraepithelial Glandular Neoplasia. (CIGN), a putative precursor of cervical adenocarcinoma. The first is a multicentre case control study of risk factors for CIGN. This employed a standard questionnaire concerning lifestyle, reproductive, sexual and contraceptive factors and a serum assay for the presence of neutralising antibodies to herpes virus. The risk factor profile obtained for CIGN indicates that it has characteristics of a sexually transmitted disease, manifestation of the disorder possibly being dependent on an altered reproductive/endocrine milieu, as indicated by associations with late onset of menarche and low parity. There was no evidence in support of an association between CIGN and oral contraceptives. With respect to identification of a possible infective agent, the study fails to provide clear evidence of an association between either HSV-1 or HSV-2 and CIGN. The second study is a multicentre prospective assessment of the effectiveness of cone biopsy as primary therapy for CIGN. Regular cytological examination was employed as a means of follow-up. Preliminary results indicate that following cone biopsy, further surgery is unnecessary when the margins of the specimen are free of atypical epithelium. To date there are no cases of residual CIGN or invasive disease in subjects so managed. The final study employs the AgNOR technique to assess the possible presence of zones of poorly recognised epithelial atypia adjacent to adenocarcinoma-in-situ/high grade CIGN. The results give no support to the presence of such areas, and thus provide further experimental support for the validity of conisation as adequate primary treatment of CIGN

Spinal T.V.T. Treated with Surgical Excision and Chemotherapy in a Dog

Background: Canine transmissible venereal tumor (TVT) is a round-cell tumor of dogs, which occurs by cell transplantation. It is usually located on the external genitalia, and is transmitted by coitus. It may occasionally be acquired by sniffng or licking the genitalia of an affected animal. Lesions may be present in the other parts of the body, such as the skin, rectum,and nasal or oral cavities. Metastasis of the TVT is uncommon, mainly occurring in immunocompromised dogs. It may affect organs such as the liver, spleen, kidney, lung, and musculature, and rarely, may be detected in the central nervous system. In this report, we describe the occurrence of a TVT causing spinal cord compression in a dog, and the results of its treatment with hemilaminectomy and chemotherapy.Case: A six-year-old male Dalmatian dog was referred to a veterinary teaching hospital with nonspecifc abdominal pain. Laboratory examination showed no abnormalities; survey radiography revealed a moderate fecal retention. The dog received painkillers and dietary guidelines. However, the patient was brought again to the veterinary teaching hospital nine dayslater with paraplegia, worse in the left limb than in the right, but with normal nociception. There was a cutaneous trunci reflex cut-off at the T10 vertebra, also worse on left side than on right, along with spinal thoracolumbar hyperesthesia. During endotracheal intubation for general anesthesia for performing a cerebrospinal fluid tap and myelography, a small mass was observed in the palatine tonsil, a sample of which was collected for cytological analysis. The cerebrospinal fluid examination showed albuminocytologic dissociation, and myelography revealed an asymmetrical epidural compression over the T8 vertebra. Surgery was performed with a lateral approach to the T8 vertebra, and a 3-cm epidural brown mass was found, which was completely excised and subjected to histopathological examination. The histopathological fndings of the mass excised from the spine revealed neoplastic proliferation of poorly differentiated, round tumor cells with large, round, central or peripheral nuclei, and slightly eosinophilic, occasionally vacuolar cytoplasm. The propagating cells formed groups separated by a delicate fbrovascular stroma, consistent with the histopathology of TVT. Upon immuno histochemical staining, the neoplastic cells were found to be positive for MHC II, CD45RA, and lysozyme, but negative for cytokeratin, CD3, CD20, and CD117. The cytological examination of the tonsillar mass confrmed TVT. The dog was treated with vincristine, but after the third cycle the treatment was discontinued due to the choice of the owner. A year after the treatment, the dog presents only a mild spinal ataxia.Discussion: Tumor cells can be transmitted through genital mucous membrane-contact at coitus. Hence, the TVT lesions are often located on the external genitalia, but this was not observed in this case. Non-cutaneous metastases, which have an incidence of about 1%, can occur on the lips and tonsils, as was observed in the present case, or in the inguinal lymphnodes, liver, kidneys, mesentery, bones, eye, brain, and abdominal cavity. The pathological characteristics of TVT is quite variable and depends on the host immune response; however, there was no evidence of immunosuppression or malnutrition in the present case. The patient might have acquired the neoplasia in the oral cavity probably from licking or sniffng the preputial or vaginal discharges of an infected dog, and therefore, the primary tumor was probably the one in the tonsil,which later metastasized to the spine. This case presents an atypically located TVT, without genital occurrence, that was successfully treated by surgery and chemotherapy. This report also indicates that TVT is also an important differential diagnosis of spinal neoplasia.Keywords: spinal neoplasms, canine transmissible venereal tumor, treatment

Predictive role of MRI and18F FDG PET response to concurrent chemoradiation in T2B cervical cancer on clinical outcome: A retrospective single center study

Tumor response in locally advanced cervical cancer (LACC) is generally evaluated with MRI and PET, but this strategy is not supported by the literature. Therefore, we compared the diagnostic performance of these two techniques in the response evaluation to concurrent chemoradiotherapy (CCRT) in LACC. Patients with cervical cancer (CC) stage T2b treated with CCRT and submitted to MRI and PET/CT before and after treatment were enrolled in the study. All clinical, pathological, therapeutic, radiologic and follow-up data were collected and examined. The radiological response was analyzed and compared to the follow-up data. Data of 40 patients with LACC were analyzed. Agreement between MRI and PET/CT in the evaluation response to therapy was observed in 31/40 (77.5%) of cases. The agreement between MRI, PET/CT and follow-up data showed a Cohen kappa coefficient of 0.59 (95% CI = 0.267\u20130.913) and of 0.84 (95% CI = 0.636\u20131.00), respectively. Considering the evaluation of primary tumor response, PET/CT was correct in 97.5% of cases, and MRI in 92.5% of cases; no false negative cases were observed. These results suggest the use of PET/CT as a unique diagnostic imaging tool after CCRT, to correctly assess residual and progression disease

The antenatal detection of asymptomatic disease

A prospective study was introduced to establish the role of the antenatal clinic as an 'early detection unit' for the screening of asymptomatic disease not specifically related to pregnancy. Patients were screened for diabetes, iron deficiency, carcinoma of the cervix, asymptomatic urinary tract infection, and vaginal disease. Four racial groups, Black, Coloured, Indian, and White, were studied. In terms of time, cost and practicability, it was found that antenatal visits could be used for screening purposes. Screening for conditions known to be prevalent among certain racial groups increases the rate of detection. Screening for asymptomatic disease during pregnancy, can be introduced easily into private practice with a minimal involvement of cost and time for both patient and doctor. The long-term benefit of the early detection and treatment of disease is discussed.S. Afr. Med. J., 48, 178 (1974)

Does Body Mass Index (BMI) Affect the Prevalence of Pap Smears?

Background The pap smear test is highly effective at detecting pre-cancerous and cancerous cervical cells. However, only 68.3 percent of women in the U.S. received a Pap smear in 2001. Previous research studies have shown that overweight and obese women are less likely to receive routine pap smears. This is especially concerning because obesity is a risk factor for cervical cancer Methods A retrospective review of data was conducted from the medical records of 90 women, 18 years of age or older, who were seen by the researcher at SMDC clinics in Deer River and Remer, Minnesota from February 2003 through May 2003. Results Bivariate analysis revealed an inverse trend between BMI levels and the prevalence of pap smears. Women in the highest BMI level were the least likely to have received a Pap smear (63.6%, n = 11). Overall, however, only 76.7 percent of all of the subjects had received a Pap smear within in the past three years. There was, however, a strong, positive correlation between Pap smears and physical exams (Pearson\u27s coefficient 0.716, p \u3c 0.001). Conclusions The results revealed that the cervical cancer screening rates for the Deer River and Remer clinics were well below the national goal (76.7% verses 90%). Even though obese women were the least likely to have received a routine Pap smear, the correlation between Pap smears and exams indicated that the providers at the Deer River and Remer clinics consistently performed Pap smears regardless of a patient\u27s body mass inde

EPMA position paper in cancer:current overview and future perspectives

At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision