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Τετάρτη 2 Ιανουαρίου 2019

Urology



A novel intraoperative physician-assigned grading score to predict postoperative return of potency at 1 year after robotic-assisted laparoscopic prostatectomy Highly accessed articlep. 61
Rajesh R Bajpai, Shirin Razdan, Marcos A Sanchez, Sanjay Razdan
DOI:10.4103/iju.IJU_158_18  
Introduction: We examined a novel method of grading nerve sparing in robotic-assisted laparoscopic radical prostatectomy to better predict the potency outcomes of patients at 1-year after surgery. This grading (scale) was based on the surgeon's criteria of intraoperative findings during completion of nerve sparing. This grading was then analyzed statistically to validate its association with potency outcomes. Methods: We devised a study module based on measurable visual cues intraoperatively where the surgeon risk stratified the surgery into four grades depending on the completeness of nerve sparing, keeping in mind the known parameters influencing potency outcomes. A novel grading scale was then proposed and used in this study for the same. We prospectively collected data and retrospectively analyzed 425 patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) at a high-volume center by a single surgeon. Results: At 1 year of follow-up, it was found that age, laterality of nerve preservation, weight of prostate, and the surgeon-assigned grading were all statistically significant independent predictors of return of potency in terms of satisfactory penetrative intercourse >50% of times and Sexual Health Inventory for Men ≥17. However, prostate-specific antigen was found not to be a predictor of the same. Conclusions: Intraoperative physician-assigned grading was found to be the single most significant predictor of the return of potency at 1-year post-RALP.
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Renal transplantation into optimized abnormal lower urinary tract – Impact on graft outcomes, patient survival, and complicationsp. 67
Selvin Theodore Jayanth, Anuj Deep Dangi, Rajiv Paul Mukha, Santosh Kumar, Santosh Varughese, Vinoi G David, Anna Valson, J Chandrasingh, Antony Devasia, Nitin Kekre
DOI:10.4103/iju.IJU_203_18  
Introduction: Literature regarding the outcomes of renal transplant in patients with abnormal lower urinary tracts (LUTs) is conflicting. The study aimed to determine the graft outcomes and complications of renal transplantation in an optimized abnormal LUT as compared to those with a normal LUT. Materials and Methods: In this single-center retrospective-matched cohort study, we identified 31 patients with an optimized abnormal LUT in our transplant database between 2006 and 2016 (Group A) and selected an equal number of matched controls (Group B). The primary outcome was graft survival, and secondary outcomes were overall survival and complications.Results: The median age was 24 years (range: 12–45), and the median duration of follow-up was 36 months in both groups. On Kaplan–Meier analysis, the estimated mean graft survival was 106 months (confidence interval [CI]: 91-120) in Group A versus 128 months (CI:117-139) in Group B (P = 0.47, log-rank analysis). On subgroup analysis of Group A, augmented bladders had the poorest mean survival (81 months, CI: 56–106), P = 0.09). The mean estimated patient survival was comparable between Group A and B (109 months, CI: 96–122 versus 139 months, CI: 134–144), P = 0.13). Infective complications (27 episodes vs. 1) and re-admissions (77 vs. 30) were significantly higher in Group A (P = 0.04 and P < 0.01). Clean intermittent catheterization was a risk factor for infections (63% vs. 37%, P = 0.033, odds ratio: 5). Conclusions: The graft and overall survival was comparable at 3 years in both groups. Infective complications were higher in Group A.
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CASE REPORTSTop

Carbon dioxide insufflation to control intractable bleeding during transurethral resection of bladder tumorp. 73
Minoru Kobayashi, Takao Kamai
DOI:10.4103/iju.IJU_263_18  
We describe a method to manage severe bleeding during transurethral resection (TUR) of a giant bladder tumor, in which vision was impaired by the bleeding. The use of carbon dioxide gas as an alternative to irrigation fluid for bladder inflation provided a better view to safely control the intractable bleeding.
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Urethral metastasis with neuroendocrine differentiation in a patient with prostate cancer treated with hormone deprivationp. 75
Karamveer Sabharwal, Anant Kumar, Andleeb Abrari
DOI:10.4103/iju.IJU_175_18  
Adenocarcinoma prostate treated with hormone deprivation may evolve into a neuroendocrine differentiated tumor. Usually visceral metastasis are seen in neuroendocrine tumors. We present a case of neuroendocrine differentiated urethral metastasis from a hormone deprived prostate cancer.
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Symmetrical peripheral gangrene of all four limbs: An unusual complication of ureteroscopyp. 78
Pankaj N Maheshwari, Nick Okwi, Anant P Pore
DOI:10.4103/iju.IJU_33_18  
Ureteroscopy (URS) is a commonly performed and a safe urological intervention. However, potentially serious infective complications are possible after URS. A young nondiabetic woman developed severe Gram-negative septicemia after ureteroscopy for a lower ureteric calculus. The sepsis progressed to symmetrical peripheral gangrene of all the four limbs. She required left below-elbow amputation, right below-knee amputation, and loss of all toes and digits of the other two limbs.
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UROLOGICAL IMAGESTop

Prominent swelling on erection: Perineal angiomyxoma as a rare entityp. 81
Shantanu Tyagi, Ravimohan Suryanarayan Mavuduru, Girdhar S Bora, Sudheer Kumar Devana, Aditya Prakash Sharma
DOI:10.4103/iju.IJU_221_18  
Perineal angiomyxoma is a rare entity, more commonly seen in females. We report a case of a 44 year old male who presented with a perineal swelling which became prominent with penile erections. Magnetic Resonance Imaging (MRI) revealed a T1 hypointense and T2 hyperintense midline lesion (4.6 × 2.5 × 5 cm) in relation to corpus spongiosum, with ill defined fat planes with the bulbospongiosus muscle and progressive enhancement on dynamic contrast sequence. A differential diagnosis of soft tissue sarcoma or hemangioma was made and the mass was completely excised via a midline perineal incision. The histopathology revealed features consistent with angiomyxoma.
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VIDEOTop

Casale's tube with VQZ stoma: An alternative to "double Monti"p. 83
Nikhil Khattar, Anurag Singla, Rajeev Sood, Arif Akhtar, Dushiant Sharma
DOI:10.4103/iju.IJU_194_18  
In situations requiring an ileal segment for performing a Mitrofanoff cathetrisable urinary diversion, occasionally a "Double Monti" is needed to achieve a length for the cathetrisable channel to conveniently reach the abdomen of an adult. Casale's tube is an alternative where it can provide a jointless tube with adequate length. The video demonstrates the procedure in an adult with a neurogenic acontractile bladder who had developed a panurethral stricture because of years of self catheterization. "VQZ" technique of stoma formation is helpful in prevention of stenosis.
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UROSCANTop

Olaparib: Transcending mutational barriersp. 85
Abhishek Chandna
DOI:10.4103/iju.IJU_292_18  
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Biochemical recurrence after radical prostatectomy: Current status of its use as a treatment endpoint and early management strategies
Barrett Z McCormick, Ali M Mahmoud, Stephen B Williams, John W Davis

Indian Journal of Urology 2019 35(1):6-17

Prostate cancer is one of the most common urological malignancies managed by a practicing urologist. Treatment strategies are varied, but radical prostatectomy (RP) remains a viable and commonly used option for many patients. A continuing challenge in the management is how to approach a patient who has biochemical recurrence (BCR) after RP. There are no consensus guidelines on the appropriate strategy, and the current recommendations, although useful, are at times confusing. The natural history of BCR is heterogeneous. Published studies aid in the clinician&#39;s ability to predict patients most likely to recur; however, this remains inexact. In addition, recent changes in the recommendations for disease screening, as well as technological advances, have added to the already challenging task of the clinician. The objective of this review is to provide an up-to-date summary of the definitions, diagnosis, and management strategies of BCR after RP. This narrative review was conducted by searching Medline for all relevant articles in English with the key terms of biochemical recurrence, prostate cancer, management, and other relevant terms. Information was compiled and reviewed for relevance to the article. Consideration was given to all articles with sufficient evidence including systematic review, retrospective studies, and clinical trials.


Female underactive bladder – Current status and management
Tammer Yamany, Marlie Elia, Jason Jihoon Lee, Ajay K Singla

Indian Journal of Urology 2019 35(1):18-24

Underactive bladder (UAB) is defined by the International Continence Society as a symptom complex characterized by a slow urinary stream, hesitancy, and straining to void, with or without a feeling of incomplete bladder emptying sometimes with storage symptoms. Until recently, the topic has received little attention in the literature probably due to a lack of consistent definitions and diagnostic criteria. We performed a literature review to identify articles related to the diagnosis and management of UAB, specifically in female patients. UAB is a common clinical entity, occurring in up to 45&#37; of females depending on definitions used. Prevalence increases significantly in elderly women and women who live in long-term care facilities. The exact etiology and pathophysiology for developing UAB is unknown, though it is likely a multifactorial process with contributory neurogenic, cardiovascular, and idiopathic causes. There are currently no validated questionnaires for diagnosing or monitoring treatment for patients with UAB. Management options for females with UAB remain limited, with clean intermittent catheterization, the most commonly used. No pharmacotherapies have consistently been proven to be beneficial. Neuromodulation has had the most promising results in terms of symptom improvement, with newer technologies such as stem-cell therapy and gene therapy requiring more evidence before widespread use. Although UAB has received increased recognition and has been a focus of research in recent years, there remains a lack of diagnostic and therapeutic tools. Future research goals should include the development of targeted therapeutic interventions based on pathophysiologic mechanisms and validated diagnostic questionnaires.


Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study
Smita Pattanaik, Harbhupinder Singh Sandhu, Ravimohan Suryanarayan Mavuduru, Shrawan Kumar Singh, Arup Kumar Mandal

Indian Journal of Urology 2019 35(1):25-33

Introduction: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. Methods: Men &#8805;45 years of age, with an International Prostate Symptom Score (IPSS) &#8805;8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. Results: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P &#60; 0.05) as compared to the baseline. However, there were no significant differences between the two drugs with respect to extent of observed effect and which drug was prescribed 1st in the sequence respectively (P &#62; 0.05). Significant period effect was observed (P &#60; 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. Conclusion: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa.


Changes in blood pressure, blood sugar, and quality of life in patients undergoing pheochromocytoma surgery: A prospective cohort study
Pradeep Prakash, Rashmi Ramachandran, Nikhil Tandon, Rajeev Kumar

Indian Journal of Urology 2019 35(1):34-40

Introduction: Pheochromocytoma surgery is associated with significant hemodynamic and metabolic changes that require post-operative monitoring. We prospectively evaluated the trends of blood pressure, blood sugar, body mass index (BMI), and quality of life (QoL) changes in a cohort of patients undergoing pheochromocytoma surgery to determine the minimum duration of monitoring and assess factors that could predict these changes. Materials and Methods: Consecutive patients undergoing surgery for pheochromocytoma over a 20-month period were included in this ethics review board-approved, prospective cohort study. Blood pressure and sugar levels were serially monitored using a fixed protocol in the perioperative period and subsequently at 3 months after surgery. BMI and QoL (using World Health Organization Quality of Life [WHOQOL-BREF] questionnaire) were recorded at baseline and 3 months. Changes were compared and assessed for the predictive factors. Results: Twenty-six patients undergoing 31 procedures were included in the study of whom 8 (30&#37;) developed hypotension and 4 (15&#37;) developed hypoglycemia after surgery. All hypotension episodes occurred within 6 hours of surgery. However, while 3 of the 4 patients who developed hypoglycemia manifest in the first 4 h after surgery, one occurred after 12 h. Occurrence of hypotension correlated with preoperative 24-h urinary vanillylmandelic acid (VMA) levels (P &#61; 0.02) and the total daily dose of prazosin (P &#61; 0.04). Out of 21 hypertensive patients, 7 (33&#37;) had persistent hypertension (HTN) at 3 months and this was associated with age (P &#61; 0.04) and diabetes mellitus (DM) at presentation (P &#61; 0.04). Among six diabetic patients, 1 (16&#37;) had persistent DM. There was significant increase in the BMI (P &#60; 0.0001) and in WHOQOL-BREF scores postoperatively. Conclusions: Hypotension occurs in 30&#37; patients and hypoglycemia in 15&#37; after pheochromocytoma surgery. Hypotension occurs immediately but hypoglycemia may manifest upto 12h after surgery. Older, diabetic patients are more likely to have persistent HTN. Surgery results in increase in BMI and improvement in QoL.


Urethral stricture after bipolar transurethral resection of prostate – truth vs hype: A randomized controlled trial
Bharath N Kumar, Anand Srivastava, Tapan Sinha

Indian Journal of Urology 2019 35(1):41-47

Introduction: Bipolar transurethral resection of prostate (B-TURP) was introduced as an alternative procedure to minimize the surgical complications of monopolar TURP (M-TURP). However, there are concerns about increased incidence of stricture urethra (SU) post B-TURP. This study was designed to analyze the incidence of SU among patients undergoing M-TURP versus B-TURP. Materials and Methods: This is a randomized controlled, single-blinded study; randomization was performed using a stratified permuted randomization algorithm (1:1 ratio) and only the patients were blinded. Both M-TURP and B-TURP were performed with a 26 Fr resectoscope; the electrosurgical generators were Karl Storz Autocon II 400 and Olympus UES-40 SurgMaster (TUR in saline [TURIS] method), respectively. Follow-up visits were scheduled at 3, 6, and 12 months post surgery and patients with lower urinary tract symptoms and a maximum urinary flow rate of &#60;10 ml/sec on uroflowmetry underwent retrograde urethrography to assess for development of SU. Results: Forty patients were randomised to each arm. None developed SU in the monopolar group, whereas there were three cases in the bipolar group (P &#61; 0.2). Among these three patients, two belonged to the failed medical management subgroup and one to the refractory urinary retention subgroup (P &#61; 1.0). Conclusion: The incidence of SU following B-TURP using the TURIS system was comparable to the conventional M-TURP. Moreover, the incidence of SU was same for both the techniques when sub-grouped according to the indication for surgery that is failed medical management versus refractory urinary retention.


Comparison of antegrade percutaneous versus retrograde ureteroscopic lithotripsy for upper ureteric calculus for stone clearance, morbidity, and complications
Amilal Bhat, Vikash Singh, Mahakshit Bhat, Nikhil Khandelwal, Akshita Bhat

Indian Journal of Urology 2019 35(1):48-53

Introduction: The optimal management of upper ureteric calculus remains controversial. We compare the outcomes of antegrade percutaneous ureterolithotripsy (APCUL) with retrograde ureteroscopic lithotripsy (URSL) for upper ureteric calculus with respect to stone clearance, morbidity, and complication rates. Materials and Methods: This prospective study was carried out from December 2014 to June 2016. A total of 117 patients with upper ureteric calculus sized (10&#8211;20) mm who underwent APCUL or URSL were included in the study. Results: APCUL and URSL were performed in 64 and 53 patients, respectively. The mean age and stone size were comparable between the two groups. The stone clearance rate at 1-month follow-up was 93.75&#37; in the antegrade group and 81.13&#37; in the retrograde group (P &#61; 0.036). Mean anaesthesia time was significantly longer for the APCUL group while the actual mean operative time was significantly longer for the URSL group (P &#60; 0.001). The overall complication rate was higher in antegrade group (P &#61; 0.804), whereas most of the major complications (Clavien Grade III or more) occurred only in the URSL group (P &#61; 0.007). Blood transfusion was required only in the APCUL group (7.8&#37; versus 0&#37;; P &#61; 0.50). In the URSL group, stone retropulsion occurred in four patients, of which three subsequently required shock wave lithotripsy and one required percutaneous nephrolithotomy in a second sitting. Conclusion: APCUL has better stone-free rates as compared to URSL for an upper ureteric calculus of size 10&#8211;20 mm. Although the postoperative minor complications are higher in the antegrade group, severe complications occurred only in the retrograde group. Hence, antegrade approach can be considered as the preferred option to achieve better stone clearance in a single sitting with acceptable morbidity and complication rates.


Are we ready for urological subspecialty-based practice in India? The resident's perspective
Ashwin Sunil Tamhankar, Ravindra Sabnis, Gagan Gautam

Indian Journal of Urology 2019 35(1):54-60

Introduction: In the current era, every broad specialty has diversified into many subspecialties including urology, which is one of the most dynamic fields. The concept of early sub-specialization relies on excelling in a niche area of interest. While this concept is appealing to the most, no formal evaluation of our residency programs has ever been conducted with regard to their adequacy in terms of equipping residents to make informed sub-specialization choices. We performed a survey amongst urological residents, in an attempt to gather information on some unanswered questions related to our residency training programs and the concept of sub-specialization. Methods: Using the Delphi principles, we conducted a survey consisting of 46 questions, amongst the Indian Urological residents (n &#61; 85), to assess the overall exposure to various subspecialties during their residency program, and the inclination of residents towards them. Results: Residents get a fair exposure to endourology, uro-oncology, female urology and reconstructive urology during their residency. However, the same did not hold true for pediatric urology, andrology and laparoscopic/robotic surgery. 90&#37; of the residents expressed an inclination towards academic practice, while 76.5&#37; were interested in sub-specialization. 60&#37; of the residents felt that they had obtained adequate exposure during residency to make a decision in this regard. Less than 20&#37; were inclined towards female urology, andrology or pediatric urology as a career option. Conclusion: There is a growing interest and inclination amongst Indian Urological residents to attain expertise in sub-specialised fields. However, our current residency programs need consolidated efforts to ensure an adequate exposure to all the aspects of Urology, especially in the subspecialties of pediatric urology, andrology and minimally invasive urology. Training should be optimized to a level, which enables the residents to take a well informed decision regarding their choice of subspecialised career path.

Liver resection for hepatocellular carcinoma in oldest old patients

Abstract

Background

For hepatocellular carcinoma (HCC), liver resection is a classical curative modality, despite its technical complexity. The incidence of HCC in the oldest old people (aged ≥ 85 years) is rising along with the global increase in life expectancy. Currently, no report has addressed liver resection for HCC in this aged population.

Patients and methods

We conducted a retrospective review of 1889 patients receiving curative liver resection for newly diagnosed HCC from 1992 to 2016. At the time of operation, 1858 of them were aged < 85 years (group A), and 31 were aged ≥ 85 years (group B). Another 18 oldest old patients, whose HCC was considered resectable but were not operated on due to the patient's refusal, served as the control group (group C). The clinicopathological characteristics and early and long-term outcomes were compared between groups A and B. All associated co-morbidities of the patients were well-treated before liver resection. The overall survival (OS) rates were also compared between groups B and C.

Result

Group B had a significantly higher incidence of associated co-morbidities and hepatitis C infection. Postoperative complication rates and 90-day mortality rates after liver resection did not differ between groups A and B (p = 0.834 and p = 1.000, respectively), though group B had a longer postoperative stay (p = 0.001). In groups A and B, the 5-year disease-free survival rates were 29.7% and 22.6% (p = 0.163), respectively, and their overall survival rates were 43.5% and 35.5% (p = 0.086). The overall survival rate of group B was significantly different from group C (35.5% vs. 0%, p = 0.001).

Conclusion

Despite a longer postoperative recovery period, liver resection for HCC in the oldest old patients may be justified if co-morbidities are well controlled.



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Specific risk factors contributing to early and late recurrences of intrahepatic cholangiocarcinoma after curative resection

Abstract

Background

Most intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy.

Methods

Included in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox's proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences.

Results

Early and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox's proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115–3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185–3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076–2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123–2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 106 IU/mL (HR = 1.785, 95% CI 1.015–3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165–5.533, P = 0.010) contributed to late recurrence independently.

Conclusion

Specific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection.



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Cytotoxic and Apoptotic Effects of Novel Pyrrolo[2,3-d]Pyrimidine Derivatives Containing Urea Moieties on Cancer Cell Lines

Background: Pyrrolo[2,3-d]pyrimidines have been recently reported to have anticancer activities through inhibition of different targets such as, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, Janus Kinase (JAK), mitotic checkpoint protein kinase (Mps1), carbonic anhydrase, MDM-2. On the other hand, aryl urea moieties which are found in some tyrosine kinase inhibitors such as Sorafenib and Linifanib have aroused recent attention as responsible for anticancer activities. The aims of this paper are to synthesize pyrrolo[ 2,3-d]pyrimidine derivatives containing urea moiety and evaluate their anti-cancer activity against human lung cancer cell line (A549), prostate cancer cell line (PC3), human colon cancer cell line (SW480) and human breast cancer cell line (MCF-7).

Methods: A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized as Scheme 1. In vitro cytotoxicity of target compounds were evaluated against, SW480, PC3, A549 and MCF-7 human cancer cell lines using a MTT assay. In order to evaluate the mechanism of cytotoxic activity of compounds 9e, 10a and 10b, having the best cytotoxic activity, Annexin V binding assay, cell cycle analysis and western blot analysis were performed.

Results: Among the target compounds, 10a (IC50 = 0.19 µM) was found to be the most potent derivative against PC3 cells. Compound 10b and 9e showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 µM and 4.55 µM, respectively. Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway.

Conclusion: Compound 9e displayed the strongest cytotoxicity against A549 cancer cell line, and induced late apoptosis in A549, as confirmed by cell cycle arrest in G0/G1 phase. In addition, compound 9e reduced expression of the anti-apoptotic protein Bcl-2 and enhanced expression of the pro-apoptotic protein Bax, besides increased caspase-9 and caspase-3, as well as cleavage of PARP levels. These results suggest that compound 9e showed a cytotoxic effect in A549 cells through activation of the mitochondrial apoptotic pathway. Further studies will be undertaken in our laboratory to improve cytotoxic activity of compound 9e and to identify the biological targets of 9e which are responsible for anticancer activity.



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Indazole Derivatives: Promising Anti-tumor Agents

Background: Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new anti-tumor agents to make up for the deficiency. Indazoles is an important class of heterocyclic compounds possessing a variety of biological activities, such as anti-tumor, anti-bacterial, antiinflammatory, anti-depressant and anti-hypertensive. This review focuses on the recent research advances of indazole derivatives in the aspect of anti-tumor.

Methods: We have searched the recent literatures about indazole derivatives from the online resources and databases, such as pubmed, scifinder and google scholar.

Results: In the recent years, many efforts have been taken to develop indazole derivatives as fibroblast growth factor receptor (FGFR) inhibitors, indoleamine-2,3-dioxygenase1 (IDO1) inhibitors, proviral integration site MuLV (Pim) kinase inhibitors, aurora kinases inhibitors, Bcr-Abl inhibitors, hypoxia inducible factor-1 (HIF-1) inhibitors and carbonic anhydrase (CA) inhibitors. Most compounds display good anti-tumor activities.

Conclusion: Developing new anti-cancer agents with new scaffolds and high efficiency is a big challenge for researchers. Indazole derivatives are a class of important bioactive compounds. Making structural modifications on active indazole derivatives according to the corresponding structure-activity relationships is of benefit to obtain more potent anti-cancer leads or clinical drugs. This review will be useful for further development of new indazole-based derivatives as anti-cancer agents.



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Molecular Characterization of Two Polysaccharides from Phellinus vaninii Ljup and their Cytotoxicity to Cancer Cell Lines

Background: Phellinus vaninii, a medicinal basidiomycete fungus, is often confused with Phellinus igniarius and Phellinus linteus. Polysaccharides extract from P. igniarius and P. linteus are reported to stimulate humoral immunity and inhibit tumor growth However, available literature reviewed no information on the relationship between bioactivities and structures of polysaccharides from the fruit body of P. vaninii.

Methods: Two water-soluble polysaccharides (PV-W, PV-B) were isolated and purified from fruiting bodies of P. vaninii by hot water and sodium hydroxide solution, respectively. The chemical structures of PV-W, PV-B were analyzed by FT-IR, GC-MS analysis and 13C NMR spectra. And, their molecular conformations were analyzed by viscosity method and SEC-MALLS-RI. Finally, their inhibition of cancer cells was investigated using MTT assay.

Results: The results illustrated that PV-W was a heteropolysaccharide, mainly composed of mannose, glucose, arabinose and galactose. PV-B was a β-1, 3-D-glucan branched with β-1, 6-D-glucose. The results of viscometry proved that PV-W and PV-B could be molecularly dispersed in water without aggregation. The results of SECMALLS- RI indicated that the two polysaccharides had the similar Mw but different molecular conformation. That is, PV-W existed as a stable globular shape, while PV-B presented a more expanded flexible random coils conformation. MTT assay indicated that PV-B showed higher inhibition effect on HepG2 and HeLa cells than PV-W in vitro.

Conclusion: This work provided the important information of active components from P. vaninii and its potential applications in the food and medicine industry.



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