A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma.

Kaposi sarcoma (KS), caused by Herpesvirus-8 (HHV-8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families. Using an rKSHV.219-infected CRISPR/cas9-model, we show that BPTFI2012T mutant cells exhibit higher latent-to-lytic ratio, decreased virion production, increased LANA staining, and latent phenotype in viral transcriptomics. RNA-sequencing demonstrated that KSHV infection dysregulated oncogenic-like response and P53 pathways, MAPK cascade, and blood vessel development pathways, consistent with KS. BPTFI2012T also enriched pathways of viral genome regulation and replication, immune response, and chemotaxis, including downregulation of IFI16, SHFL HLAs, TGFB1, and HSPA5, all previously associated with KSHV infection and tumorigenesis. Many of the differentially expressed genes are regulated by Rel-NF-κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation-mediated monogenic hereditary predilection of KSHV virus-induced oncogenesis, and suggest BPTF as a drug target.

[PRIMARY GASTRIC PLASMACYTOMA IN A BREAST CANCER MALE PATIENT].

INTRODUCTION: Plasmacytoma is a malignant tumor of the plasma cells. Extra-medullary plasmacytoma is rare and with an even lower incidence appears as a primary tumor of the stomach. Initial onset of the disease in the upper gastrointestinal tract is reported in the literature as just second to primary plasmacytomas of the head and neck system. The presenting symptoms are related to the organ involved and systemic symptoms can be weight loss, pain, bleeding and even fever. As this is a rare disease, there is no standard treatment and patients undergo endoscopic resection or chemotherapy with or without additional radiation. The prognosis of the disease depends on the possible future diagnosis of multiple myeloma which can be up to 50% within only a few years. We hereby report a case of a male patient with a past locally advanced breast cancer who was on prolonged adjuvant hormonal treatment. He developed a new symptom of melena and underwent a thorough evaluation including imaging and repeated biopsies from a large gastric lesion. The results were inconclusive mainly because of the differential diagnosis between breast cancer metastases and a new second primary malignancy. In view of a clinical deterioration and lack of diagnosis, an operation of radical gastrectomy was eventually performed only to surprisingly diagnose a rare hematologic disease of the stomach - gastric plasmacytoma. This diagnosis is rare in itself, especially having his previous male breast cancer and maternal multiple myeloma. The diagnostic procedure in this case had also provided the full treatment for his illness.

Treatment of cervix carcinoma FIGO IIIb with Photofrin II as a radiosensitizer: a case report.

Cervical cancer is the fourth-most common type of cancer and cause of death in women. Human papilloma virus (HPV) infection is responsible for over 90% of cervical cancers. The recommended treatment is multidisciplinary, consisting of a combination of surgery, chemotherapy, and radiation therapy. The standard treatment in advanced stages, such as FIGO IIIb, is radio-chemotherapy with overall 5-year survival of 32%. Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models, admitted for radiation therapy. We describe a patient with advanced cervical carcinoma (squamous cell) who contacted us for further therapy in 2003. Staging included a gynecological examination, colonoscopy, explorative laparotomy, biopsy and pelvic MRI. The explorative laparotomy showed enlarged pelvic and para-aortal lymph nodes. The histologic examination described tumor infiltrated, positive lymph nodes (Stage FIGO IIIb). Contrary to recommendations, the patient refused standard treatment with a combination of chemotherapy and radiotherapy, but accepted a combined treatment of Photofrin II as a radiosensitizer and a radiotherapy procedure. She underwent irradiation with a 50.4 + 14 Gy boost with fractionation of 1.8 Gy day-1 for 5 days per week; the boost was given with 2 Gy fractions. She was injected with a single intravenous dose in a slow infusion (30 min) of 1 mg kg-1 of Photofrin II 24 h prior to radiation therapy. A localized relapse in the cervix appeared after 30 months, and was resected by hysterectomy. The patient is still alive with no evidence of disease after 15 years.

An update on Curcuma as a functional food in the control of cancer and inflammation.

PURPOSE OF REVIEW: Curcumin, commonly known as turmeric, is a spice that comes from the root Curcuma longa. The present article presents an update of new studies of curcumin activities as tested in anticancer models from 2011 to 2015. RECENT FINDINGS: Evidence from in-vitro and in-vivo research, together with clinical trials conducted over the past few decades, substantiates the potential of curcumin as an anticancer and anti-inflammatory agent. The development of formulations of curcumin in the form of nanoparticles, liposomes, micelles, or phospholipid complexes to enhance its bioavailability and efficacy are still in the early stages. Clinical trials with curcumin indicate safety, tolerability, and nontoxicity. However, the efficacy is questionable, based on the small numbers of patients in each study. SUMMARY: The laboratory and the clinical studies until 2011 were summarized in a review published in this journal. An update of the new studies and knowledge from 2011 to March 2015 focuses on new ways to overcome its low bioavailability and data from clinical trials.

Assessment of Predictors for SARS-CoV-2 Antibodies Decline Rate in Health Care Workers after BNT162b2 Vaccination-Results from a Serological Survey.

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020−August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (ß = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings.

Regional hyperthermia combined with chemoradiotherapy in primary or recurrent locally advanced pancreatic cancer : an open-label comparative cohort trial.

PURPOSE: To evaluate the therapeutic effect of delivering regional hyperthermia (HT) plus chemoradiotherapy (CRT) in patients suffering from locally advanced unresectable pancreatic cancer (LAPC). METHODS: Between January 2000 and December 2008, 68 patients affected by primary (56/68) or recurrent (12/68) LAPC were treated either with CRT alone or CRT plus HT. Radiotherapy (RT) consisted of 3D conformal irradiation of tumor and regional lymph nodes (dose ranged from 30 Gy/10 fractions to 66 Gy/33 fractions). Chemotherapy (CT) consisted of gemcitabine (GEM) alone or in association with either oxaliplatin, cisplatin, or 5-FU. HT was delivered twice a week, concomitant with RT. RESULTS: In the current study, 60 of the original 68 patients were included. Median overall survival (OS) was 15 months in the HT group versus 11 months in the control group (log-rank test: p = 0.025). HT did not increase CRT toxicity. CONCLUSION: HT can be added safely to CRT in LAPC, thus, resulting in slightly prolonged survival in certain cases.

Curcuma as a functional food in the control of cancer and inflammation.

PURPOSE OF REVIEW: Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Turmeric is a spice that comes from the root Curcuma longa. Extensive research over the past half century and especially in recent years has revealed important functions of curcumin and a timely review of clinical state-of-the-art using curcumin. RECENT FINDINGS: In-vitro and in-vivo research has shown various activities, such as anti-inflammatory, antiviral, antifungal, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and antiangiogenic properties. Curcumin also have been shown to be a mediator of chemo-resistance and radio-resistance. SUMMARY: Various in-vitro and in-vivo and scarce number of clinical studies on curcumin were identified. The various effects and properties of curcumin are summarized in this review, including preclinical and especially clinical studies. This review concentrates on recent knowledge and research with curcumin clinical applications, and clinical studies, focusing on studies published between 2008 and 2011 demonstrating the gap between preclinical and clinical research.

Curcumin and gemcitabine in patients with advanced pancreatic cancer.

Curcumin has a potent antiproliferative activity and can also potentiate the antitumor effect of gemcitabine. This study was undertaken to evaluate the activity and feasibility of gemcitabine in combination with curcumin in patients with advanced pancreatic cancer. Seventeen patients were enrolled in the study and received 8,000 mg of curcumin by mouth daily, concurrently with gemcitabine 1,000 mg/m(2) IV weekly × 3 of 4 wk; 5 patients (29%) discontinued curcumin after a few days to 2 wk due to intractable abdominal fullness or pain, and the dose of curcumin was reduced to 4,000 mg/day because of abdominal complaints in 2 other patients. One of 11 evaluable patients (9%) had partial response, 4 (36%) had stable disease, and 6 (55%) had tumor progression. Time to tumor progression was 1-12 mo (median 2½), and overall survival was 1-24 mo (median 5). Low compliance for curcumin at a dose of 8,000 mg/day, when taken together with systemic gemcitabine, may prevent the use of high doses of oral curcumin needed to achieve systemic effect. Further studies should be conducted to evaluate the ability of other formulations of curcumin to enhance the effect of chemotherapy in cancer patients.

Erratum: Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

[This corrects the article DOI: 10.3892/mco.2019.1921.].

[Self-expanding oesophageal stents: comparison of Ultraflex and Choostent]. / Endoprotesi esofagee autoespansibili: studio di confronto tra Ultraflex e Choostent.

Two types of covered self-expanding metal stents were compared in a consecutive series of 57 patients. Stent placement was successful in all patients. No procedure-related deaths were observed. The overall hospital morbidity was 7%. No significant differences in the efficacy of palliation of dysphagia, rate of complications, and survival rates were seen using the two types of stent. An endoscopic reintervention was required in 14% of the patients. Both stents proved to be safely removable in the short term follow-up, and the benefit of temporary insertion was documented in patients with primary oesophageal neoplasms prior to chemotherapy or chemoradiation therapy and in those with anastomotic strictures/leaks. A multidisciplinary strategy, guided by the concept that a stent should not represent the only, definitive treatment modality, may improve the quality of life of patients with advanced oesophageal carcinoma.

Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

Goblet cell carcinoid or carcinoma (GCC) is a rare tumor found incidentally during routine management of acute appendicitis. GCCs are more aggressive compared with conventional appendiceal tumors but less aggressive compared with adenocarcinomas, and they often present with serosal and mesoappendiceal involvement. We herein report two cases of acute appendicitis in a 45-year-old female and a 60-year-old male with varied clinical symptoms. Pathological examination of the appendix revealed the presence of adenocarcinoma with goblet cells and a Ki-67 index of 25% (grade 3) and 15% (grade 2), respectively. Subsequent right hemicolectomy was performed according to the current guidelines. No signs of disease recurrence or metastasis were detected during regular follow-up. However, the lack of a standardized classification system for GCC and the discrepancies in specific reliable markers renders their prognostic and predictive value in GCC at diagnosis insufficient. The present study also aimed to address current concerns regarding the diagnosis, treatment and prognosis of GCC, as well as the need to review and update current guidelines. To conclude, proper clinical management and the prediction of outcome for patients with GCC varies according to the classifications or staging criteria used by the clinicians; hence, a review of the current guidelines should be considered.

Management of Peripheral Neuropathy Induced by Chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is considered a severe side effect of therapeutic agents with limited treatment options. The incidence of CIPN in cancer patients is approximately 3-7% in cytostatic monotherapy and as high as 38% in cases of polychemotherapy. The prevalence of CIPN was found to be 68% within the first month of chemotherapy treatment. In some cases, CIPN can resolve, partially or completely, after completion of the treatment; in other cases, it can remain for a long time and affect the patient's quality of life. OBJECTIVE: The aim of this study is to present up-to-date data regarding available treatment options for the management of CIPN. MATERIALS AND METHODS: The up-to-date guidelines of ESMO (European Society for Medical Oncology), ASCO (American Society of Clinical Oncology), ONS (Oncology Nursing Society), NCI (National Cancer Institute), and NCCN (National Comprehensive Cancer Network) were reviewed and included in the manuscript. RESULTS: The use of tricyclic antidepressant (TCA), selective serotonin norepinephrine reuptake inhibitor (SSNRI), pregabalin, and gabapentin are recommended as first-line treatment. Other treatment options were offered as second and third lines of treatment (lidocaine patches, capsaicin high-concentration patches, tramadol, and strong opioids, respectively); however, lower significance was demonstrated. Inconclusive results were found in the use of cannabinoids, drug combinations, antiepileptics, antidepressants, and topical drugs. CONCLUSION: TCA, other antidepressants, and opioids could be recommended as treatment. Yet, we could not recommend an ideal therapeutic agent for the prevention or treatment of CIPN. Therefore, CIPN continues to be a challenge to clinicians and our patients.

Cancer stem cells: how can we target them?

One of the most exciting concepts being explored in cancer research today is the idea of cancer stem cells. Evidence for the existence of such cells was first proposed for haematological malignancies and, more recently, for solid tumors, including breast, brain, colon and pancreatic cancer. The cancer stem cell hypothesis states that a minority of transformed stem cells, or progenitors with acquired self-renewal properties, are the source of tumor cell renewal and thereby determine the behaviour of tumors, including proliferation, spreading and response to chemo- and radiotherapy. Indeed, just as somatic stem cells may be resistant to the induction of apoptosis by cytotoxic agents and radiation therapy, cancer stem cells may display increased resistance to these agents as compared with the more differentiated cells that comprise the mass of tumors. More specifically, the reactivation of varied developmental signalling cascades (epidermal growth factor (EGF)/EGFR, stem cell factor (SCF)/KIT, sonic hedgehog, Notch, and/or Wnt/beta-catenin) combined with the increased DNA repair mechanisms and ABC transporter-mediated drug efflux in cancer stem cells may be responsible for their resistance to conventional therapies. Furthermore, changes in the local microenvironment of cancer stem cells may also influence their behaviour. Thus, the molecular targeting of such highly tumorigenic cancer cells must be considered for improving the efficacy of the current anti-cancer strategies with the aim to sensitize tumors toward conventional therapies and effectively abrogate tumorigenesis. This review provides a summary of some developments in the field of cancer stem cell targeting and highlights aspects where it could be of help in the drug discovery process.

Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials. OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly. METHOD: Systemic compilation of the relevant literature. RESULTS & CONCLUSION: Today's treatments cannot cure GBM patients but only extend their overall survival. The use of chemoradiation, immunotherapy, and radio sensitizers as an adjuvant therapy cannot reduce the high rates of recurrence within a few months after treatment. Radiotherapy will remain the backbone of the treatment but new treatment modalities must be developed.

The Possible Role of Infertility Drugs in Later Malignancy: A Review.

BACKGROUND: Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility. OBJECTIVE: To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs. METHODS: Systematic compilation of the relevant literature. RESULTS & CONCLUSION: Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies.

Clostridium difficile Infection: Associations with Chemotherapy, Radiation Therapy, and Targeting Therapy Treatments.

BACKGROUND: Although mucositis, diarrhea, and constipation as well as immunosuppression are well recognized side-effects of cancer treatment, the underlying mechanisms including changes in the composition of gut microbiota and Clostridium difficile infection have not yet been thoroughly reviewed. OBJECTIVE: We herein set out to review the literature regarding the relations between cancer chemotherapy, radiation treatment, and Clostridium difficile-associated colitis. METHOD: Review of the English language literature published from 2008 to 2015 on the association between cancer chemotherapy, radiation treatment, and C. difficile-associated colitis. RESULTS: Certain chemotherapeutic combinations, mainly those containing paclitaxel, are more likely to be followed by C. difficile infection (CDI), while some tumor types are more likely to be complicated by CDI following chemotherapy. CDI following irradiation occurs mostly in patients who were treated for cancer in the head and neck area. Risk factors found were proton pump inhibitors, antibiotics, cytostatic agents, and tube feeding. The drug of choice for an initial episode of mild-to-moderate CDI is metronidazole, whereas vancomycin is reserved for an initial episode of severe CDI. Fidaxomycin is another option for treatment of severe CDI, with fewer recurrences. CONCLUSION: The influence of CDI on the treatment of oncological patients is not fully acknowledged. Infection with C. difficile is more frequent in those patients treated by antibiotics simultaneously with chemotherapy. Aggressive supportive care with intravenous hydration, antibiotics, and close surgical monitoring for selective intervention can significantly decrease the morbidity and life-threatening complications associated with this infection.

Development of an HPLC method for monitoring of Photofrin II therapy.

OBJECTIVES: To develop and to validate a method to quantify plasma porphyrins after application of Photofrin II, a drug preparation that is used for photodynamic therapy (PDT) and as a radiosensitizer. DESIGN AND METHODS: After solid phase extraction of postdose plasma samples, reversed phase high performance-liquid chromatography with fluorescence detection was performed. Plasma porphyrin concentrations were monitored in five patients that were treated with Photofrin II. RESULTS: The method proved linear over a wide concentration range, precise, and applicable in a routine clinical laboratory setting. CONCLUSIONS: The method described here will enable large-scale clinical pharmacokinetic studies on Photofrin II; investigations can now address possible correlations between individual concentrations of drug-derived plasma porphyrins and systemic photosensitivity--representing the main side effect of Photofrin II--with the perspective of individualized light protection regimens after Photofrin II administration.

Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Preliminary results.

AIMS AND BACKGROUND: Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer. MATERIALS AND METHODS: For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation. RESULTS: 5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days. CONCLUSION: Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.

Optimized radiation of pelvic volumes in the clinical setting by using a novel bellyboard with integrated gonadal shielding.

The purpose of this study was to determine the feasibility of a custom-made, modified bellyboard to reduce radiotherapy side effects on small bowel, bladder, skin, and male gonads. Two groups of 10 consecutive patients each were treated from January 2003 through April 2003 with neoadjuvant (45 Gy) or adjuvant (54 Gy) radio(chemo)therapy in single fractions of 5 days a week 1.8 Gy for rectal carcinoma, using a photon energy of 15 MV. One group was positioned in a prone position without an immobilization device, the other group was positioned on our bellyboard. Treatment planning was calculated by using a 4- and a 3-field box technique. Differences in the dose of organs of risk were calculated. For 1 male patient, a gonadal shielding was developed and integrated. All patients examined with the bellyboard demonstrated an anterior and cranial dislocation of the small bowel. Using a 4-field box, the mean dose to the small bowel of patients treated on our bellyboard was 56.5% as compared to 63.1% when treated without the bellyboard. When a 3-field box was used, the mean dose to the small bowel was 52.4% when the bellyboard was used, as compared to a mean dose of 63.1% without the bellyboard. Regarding the dose volume effects to the bladder, the mean dose for patients treated with a 4-field box was about 14.5% higher as compared to patients treated with a 3-field box. The mean dose to the hip joints and skin also depended on the radiation technique. The patient who received gonadal shielding received a maximal total gonadal dose of about 75.0 cGy in single fractions of maximal 3.0 cGy (TL-dosimeters). Daily setup variations evaluated by a beam's-eye view were similar in both groups and ranged from 0.5 cm 1.0 cm. For daily use, our bellyboard appears to be an ideal compromise due to effectiveness, its easy handling, and reproductive positioning; moreover, it can also be used in combination with gonadal shielding.

Is the clinical use of cannabis by oncology patients advisable?

The use of the cannabis plant for various medical indications by cancer patients has been rising significantly in the past few years in several European countries, the US and Israel. The increase in use comes from public demand for the most part, and not due to a scientific basis. Cannabis chemistry is complex, and the isolation and extraction of the active ingredient remain difficult. The active agent in cannabis is unique among psychoactive plant materials, as it contains no nitrogen and, thus, is not an alkaloid. Alongside inconclusive evidence of increased risks of lung and head and neck cancers from prolonged smoking of the plant produce, laboratory evidence of the anti-cancer effects of plant components exists, but with no clinical research in this direction. The beneficial effects of treatment with the plant, or treatment with medicine produced from its components, are related to symptoms of the disease: pain, nausea and vomiting, loss of appetite and weight loss. The clinical evidence of the efficacy of cannabis for these indications is only partial. However, recent scientific data from studies with THC and cannabidiol combinations report the first clinical indication of cancer-related pain relief. The difficulties of performing research into products that are not medicinal, such as cannabis, have not allowed a true study of the cannabis plant extract although, from the public point of view, such studies are greatly desirable.